When a father is killed in a home invasion, Don and his team investigate the connection between the murder and a rash of robberies in the upscale community.

Megan feels responsible for an agent's death following an explosion at a meth house the FBI had targeted for a bust. When the kingpin eludes capture, it's discovered he may also be involved in child pornography when one of the photographs on his computer turns out to be a young girl in a sexually explicit position. The picture sends Charlie on a crusade of his own, as he remembers a girl he knew as a young child that he suspected was being abused, and he's determined to save the little girl in the picture.

After four people nearly die from poisoning, Don learns someone is tampering with nonprescription drugs. When the perpetrator publishes a manifesto in a local paper, Don is led to believe the person may be a former employee of the drug company that manufactured the drug.

An arsonist sets a fire at a car dealership that kills a sales person. The name of an extremist environmental group is spray-painted on the scene, but the group denies involvement. It becomes Don's task to determine whether the group or someone else is responsible. Charlie is called in to help figure out if there is a pattern to the fires that would help provide a profile of the arsonist.

A murder investigation at a Los Angeles card club leads the FBI to a complicated card-counting scheme involving college students.

When a DNA synthesizer with the capability of customizing diseases is stolen from the campus where Charlie teaches, Don fears the thieves may be terrorists out to start or advance a bio-warfare program and also believes the theft was an inside job.

Don and his team investigate an anti-war bombing outside an Army recruiting center that resembles the work of a 1970s anti-war activist who disappeared 30 years earlier after being accused of planting a bomb that killed two people. Retired Agent Thomas Larson, who tried to solve the case 30 years ago, returns to help but questions Don's loyalty when it is revealed Alan knew the radical activist and participated in demonstrations with him, thus causing tension within the family.

Don and his agents are asked to investigate when a search team finds three dead women in the wilderness who were apparently murdered under bizarre circumstances. The case becomes more suspicious when Don learns the search team was led to the crime scene by a psychic. When the psychic offers to help the FBI in solving the crime, Charlie is determined to prove the psychic is a fraud.

In an effort to find the murderer of an Iraqi woman who had been making a documentary that promoted the rights of Muslim women, Don enlists the help of the victim's cousin. Through her cousin, Don uncovers a connection to Saddam Hussein.

Back at home, Charlie rekindles a romantic relationship with a former girlfriend when she visits him while on a book signing tour.

Don and his team investigate a school shooting. He learns two students could have a strong motive, so Charlie uses the school's radio frequency identification system to track the shooters' movements through the school's hallways. When Charlie detects an abnormal pattern, the agents take a look at the evidence and discover a third participant no one had suspected earlier.

When an ATF agent is found dead under unusual circumstances, Don wants to take the case, which revolves around an elaborate bank robbery, after he learns the victim was his former girlfriend. He then becomes quite introspective as he realizes the impact his career has had on his personal life and decides to turn his attention toward a new woman.

When an assailant opens fire in the FBI offices, Don and his team must determine his motive and possible connection to a dangerous arms dealer who is on trial. After nearly getting shot, Charlie is shaken and reluctant to return to the offices, which hinders his contribution to the case.

The FBI becomes involved when the bodies of young Asian girls are washed up on the beach. The situation becomes more critical when it is discovered one girl has avian flu. As the investigation continues, Don and his team discover a connection between the girls and the sex trade industry. Meanwhile, Amita considers a transfer to Harvard University, which causes Charlie to re-evaluate his feelings for her.