David interrogates Billy Rivers, one of Crystal Hoyt's ex-boyrfriend and someone she was looking for. When Billy is not cooperating as they would like, the team digs up some dirt on his attorney. The team must work harder and faster when one of theirs is taken by Crystal. Meanwhile, Alan contemplates getting his own place and moving out of the family homestead. Amita eschews the position at Harvard and accepts one at CalSci.

The FBI faces a stand off with Crystal who refuses to let Megan go unless the FBI releases her boyfriend in exchange. During the wait, however, Megan manages to get Crystal to open up about her motive, which triggers a violent reaction and puts Megan in even more danger. Don wrestles with his conscience about decisions he made in an effort to rescue Megan. Charlie and Amita decide to give romance a second chance, now that Amita is remaining at CalSci. Alan decides to stay put for the time being as he thinks he'll miss Charlie and Don. Larry feels guilty at not preventing Megan's ordeal.

A very valuable painting on loan from a private collector is stolen from a small museum desipte stringent security measures. At first it seems to be a simple theft or insurance scam. As Charlie begins to research the provenance of the painting, he discovers that it was stolen by the Nazi's during the Holocaust, causing Don to refocus his approach to the case. Alan and Charlie are at odds over household chores and maintenance.

As Charlie's mathematical analysis reveals that the victim's death was no mere accident, Don grapples with the possibility of a leak in the Department of Justice. Meanwhile, Colby is caught trying to protect his old military buddy who has come under suspicion in the case, causing Don to question Colby's loyalty. Charlie is miffed at Larry because Larry chose another mathematician to collaborate on a paper he published.

When a father driving with his two children is gunned down on the freeway, Megan is puzzled when she can't find a specific pattern to the suspect's behavior and goes to Charlie for some insight. But as additional freeway incidents occur, Don uncovers an unlikely clue that may lead them to the killer. Amita seeks Larry's advice on making the transition from graduate student to faculty member. Charlie becomes concerned when he learns that Larry has been sleeping on his couch and living in his office.

When Don and his team investigate a murder at a horse track, they stumble onto more than just a plot of betting on fixed races. As Charlie digs deeper into the victim's life and discovers an elaborate gambling scheme, he realizes he has only uncovered part of the crime. Soon, he discovers a connection to a third party sending the case in a whole other direction. Larry becomes increasingly distracted by the lack of structure in his relationship with Megan.

When a series of blackouts occur in power stations leaving large areas of Los Angeles in the dark, Don and his team must determine if the blackouts are accidental or the work of terrorists. In a surprising development, the blackouts are related to a complicated scheme concerning a previous case.

After some probing into the case, Charlie is astonished when he discovers Oswald Kitner, a fantasy league player who has developed an extraordinary statistical analysis that identifies which players use steroids. This unforeseen breakthrough leads the FBI to a possible motive and potential killer. Unfortunately, someone does not want the pioneering statistical methods to see the light of day, putting Oswald and Charlie in danger.

Don and his team investigate a trail of illegal waste disposal after a sinkhole, which collapses in a school playground, kills an elderly woman and injures several children. This episode introduces Kathy Najimy as Dr. Mildred Finch, Charlie Eppes' new department chair. At her welcoming reception, Dr. Finch immediately hits it off with Charlie's father, Alan. She then proceed to irritate Charlie, Amita, and Larry by assigning them additional academic committee obligations.

A California State Senator and a psychiatrist--neither have much in common with the other except for one thing...they both turn up dead on Don's watch. While the circumstances of their deaths are different, Don thinks the two murders are related, and tries to prove his hunch right. What he finds may bring to light a deep secret the government has been hiding for years.

Don hunts for a serial killer after a man is found tied up and beaten to death in an unoccupied house that is for sale, the third such murder to occur in six weeks. The investigation reveals that all three victims may have met their killer through Internet chat rooms and were lured to the houses with the promise of having sex with an underage girl. Also, Larry learns that he may be pulled from NASA's space mission because of his recent bizarre behavior.

When a teenage girl is found almost beaten to death, Don and his team discover that she escaped from a polygamous cult headed by a fundamentalist leader who is on the run from the FBI. They discover that the girl's mother, who is also a religious zealot, gave her daughter to the leader. As their contribution to the investigation, Charlie and Amita try to decipher a chart that was found at the leader's last known location, hoping it will lead them to him. Millie provides them with a surprising answer. When Charlie and Amita return prematurely from a math conference to work the investigation, they find Alan and Millie sharing a bottle of wine in the Eppes homestead.

The FBI asks Charlie to retrace the path of a marine salvage barge because Don suspects a murder took place on board. However, Charlie is put in a difficult situation when the National Security Agency (NSA) also requests his help to find the yacht for the confidential case they are working on. Meanwhile, Liz and Don try to figure out a way to make their personal relationship work after she is permanently transferred to LA. Meanwhile, Alan and Millie's relationship continues to develop. Millie prepares to challenge Alan at chess.

Don and his team investigate a rash of deadly restaurant robberies. During the investigation, the FBI discovers that the thieves steal the restaurant customer's credit cards so that they can run up charges at a fake Internet store and then route the money to offshore accounts. Charlie tries to pinpoint where the money is being laundered to prevent more restaurants from being hit. Meanwhile, in the wake of the Crystal Hoyle shooting, the FBI forces Don to talk to William Bradford, an occupational psychologist and FBI consultant whose specialty is trauma recovery. Back on the CalSci campus, Dr. Finch attempts to twist Charlie's arm into particpating in a lucrative grant project sponsored by a pharmaceutical company despite Amita's reservations concerning the company's business practices in the third world.

The authorities looking into a case are lead to believe that a former gang member was behind a police officer's death, a death they think was a revenge killing for the death of the former gang-member's brother. However, when Charlie gets a hold of and analyzes the data, his findings lead the FBI through a tangled web of suspects and dirty cops. Meanwhile, Don and Liz's relationship moves to the next level. In other developments, Alan Eppes is sued for a driving range project he designed that has become a neighborhood nuisance. Dr. Mildred Finch asssts him in finding out what went wrong and who is responsible.

While training for an upcoming championship match, a martial arts fighter dies in the ring. The case becomes more complex when the victim's sparring partner, a friend of David's, emerges as the prime suspect. Meanwhile Charlie has to contend with a competing professor's psychological warfare while he is preparing to defend Dr. Fleinhardt's seat at the final table of the poker championship while he's aboard the international space station.

Don has another visit with his therapist while the team must race against the clock to find a young boy who has been kidnapped. Those behind the kidnapping refuse to release the boy until the $3 million ransom is met.

Several suspicious deaths of people in similar careers are found to be connected to an electronic voting fraud conspiracy. Don and the FBI team, with the help of Charlie, must track down those behind the conspiracy before more are killed. A well-connected billionaire seems to be at the center of the scheme. Sabremetics whiz-kid Oswald Kitner returns to assist Charlie with the statistics based mathematics aspects of the case.

A small plane crashes mysteriously in a forest, killing all on board. Amita & Dr. Finch help Charlie repair the plane's black boxes. When Charlie is able to test the in-flight computer, he uncovers the surprising truth behind the crash. Meanwhile, Charlie is also busy tracking down a burglar after his house is broken into.

While on the hunt for a serial letter bomber, Don and Charlie disagree over whether a suspected bomber, who had eluded conviction years earlier, is the person responsible for the latest murder. Complicating the situation, they both have to cope with an over-zealous ATF agent who is hell-bent on railroading the suspect despite only flimsy circumstantial evidence. Meanwhile Alan and Millie bet one another they can each go for 30 days without buying a new consumer item, only food and necessities.

Don believes that a death row inmate has an ulterior motive when he suddenly wants to confess the whereabouts of bodies he buried during his days as a hit man for the mob. Dr. Larry Fleinhardt returns to Earth from his mission aboard the International Space Station. He brings back an Aztec kipu (macrame necklace) that he made in orbit along with a phobia of enclosed spaces. Dr. Finch wants to throw him a big party, but Larry wants to keep a low profile. After a low-key welcome home dinner at the Eppes', he reveals that he's going to take up residence at a near-by Bhuddist monestary for the time being.

Don and the FBI uncover a possible terrorist attack on Los Angeles that targets the city's water supply. Much to Don's dismay, Charlie gets their father, Alan, more involved in the investigation than Don is comfortable with.

When thieves hijack a truck filled with valuable medical supplies, $50 million dollars intended for a relief effort in Zambia and two aid workers, the FBI races a second violent crew intent on getting to the goods first. Charlie agrees to a joint session with Don and his therapist to discuss issues that arose during their childhood.

Following a deadly standoff with a mysterious bomber, Don and Charlie learn that he was poisoned in order to keep him from revealing a secret that changes the FBI team forever.