Lionel conspires with his old friend Morgan Edge, who arranged for Clark's vial of blood to be stolen. He retrieves the sample and uses the vial in an attempt to cure his terminal liver disease, testing the treatment on a new subject, Adam Knight. When Chloe and Lex learn that Lionel killed his parents, Lionel conspires to make it look like Lex has a psychotic break and institutionalizes him, where he gives him a treatment to make him forget Lionel's misdoings. However, Lex is brought back home where he undergoes several psychiatric evaluations. In attempt to get rid of witnesses for his impending trial, Lionel plans attempts on Chloe and Lex's life.
Lex Luthor returns from the dead and faces his father and his wife. Clark also returns to Smallville and tries to repair his relationships with Lana and Chloe. Morgan Edge follows Clark to Smallville demanding the package Clark stole for him.
Van McNulty is avenging his father's murder by killing metahumans. Clark is shot with a kryptonite bullet. Lana has to deal with her growing prejudice against kryptonite-infectedpeople, and Lex decides that his own physiology might be responsible for his uncanny ability to cheat death.
Sarah Conroy moves in next door and immediately enters Clark's dreams. Clark and Lana learns that she is being artificially kept in a coma by her uncle who controls the money only as long as she lives incapacitated. While, Lionel demands that Lex undergo a full psychological evaluation.
Perry White arrives in Smallville in search of alien stories for a tabloid news show. He devises a dangerous scheme to expose Clark's superpowers, and Lex learns that Perry has powerful incriminating evidence of Lionel's shady past.
Clark discovers that Jor-El was on Earth forty years ago. Lana helps Clark discover the truth about who killed her great Aunt Louise. Lex learns that his grandparents were murdered, and he begins to suspect his father.
Clark is jealous and suspicious when Lana suddenly becomes attracted to Seth Nelson and begins to act rebelliously. Meanwhile, Lex discovers Chloe has been investigating his father and offers her his protection.
Lex has been suffering for a month in Belle Reve, but when Lionel orders radical electroshock therapy, Clark finally decides to throw caution to the wind and break him out. Unfortunately, Van, Ian and Eric are ready to take him out. Meanwhile, Lana meets Adam Knight during her physical therapy.
Clark is temporarily blinded by his own heat vision reflected through kryptonite. He develops super-hearing to compensate. While Nathan Dean kidnaps Pete, Lex fires Chloe's dad, and Lana tells Clark she is seeing someone new.
Coach Altman is so distraught over his daughter's death that he tries to kill Lana, himself and Megan Calder. Jordan Cross foresees their deaths and enlists the aide of Clark to thwart the plan. Meanwhile, Chloe spies Adam Knight taking drugs, and Lex discovers something, too.
Jason Dante threatens to kill Pete Ross. Clark has to lie, steal and cheat to save his friend. While Lana discovers that Adam Knight is Chad Nash, Chloe discovers that he is taking a serum of strange platelets, and Lex blackmails his physician, Lia Teng.
Garrett Davis is holding hostages at the hospital until his brother receives a new liver. Clark steals a vial of a serum, which may revive him. Lana tells Clark Adam Knight's secret, and Lex tracks down Lia Teng.
Clark discovers that Jor-El is sending Jonathan messages through the key. Lionel makes a deal with Dr. Swann. Meanwhile, Lex continues helping the FBI investigate Lionel, and Lana gives up on a relationship with Clark.
Jeremiah Holdsclaw steals Palak from the Kawatche Caves and receives super powers leading him to believe that he is Naman. Clark must stop him before he kills Lionel. Meanwhile, Lex and Lana sell the Talon, and Chloe discovers that Pete's parents are divorcing.
Emily Dinsmore returns to prevent Lana's departure to Paris. Clark decides to tell Lana his secret to prevent her departure to Paris. Pete decides to move to Wichita after Frank Loder tries to beat Clark's secret out of him. While Chloe finally comes through for Lex, and he restores her deleted voice mail confession from Lionel.
Kara comes to entice Clark to return to Jor-El. Jonathan reveals the deal he made with Jor-El. Lionel helps Clark discover Lex's room of obsession, and Lana leaves for Paris. Meanwhile, Lionel is denied bail, but Chloe and her father are killed in an explosion.