Distraught over her break-up with Clark, Lana goes to a rogue medical student who experiments with a dangerous kryptonite-based serum that allows people to flat-line but see their dead loved ones. Lana attempts to see her dead parents using the serum and when Clark returns from Honduras to help her, the doctor injects him with the serum and Clark speaks with his dead father...who warns him that Lionel knows his secret. Meanwhile, Lionel continues working to get closer to Martha, and Lex has a near-death vision of his mother.
Clark discovers that the new assistant at the Daily Planet, a bespectacled, bumbling woman named Andrea, is actually a mysterious female vigilante who stalks Suicide Slum. Her path crosses Clark's as they both seek the same criminal. Meanwhile, Clark's bottled-up grief threatens to get the best of him and LuthorCorp experiences a shakeup.
The Senatorial race between Jonathan and Lex heats up when Jonathan receives an anonymous threat warning him to drop out of the election. When Clark finds Jonathan badly beaten he determines to find the attackers. Lois is thrown into the mix when she is captured and she is forced to assassinate Jonathan during his speech.
Lex is given an envelope with damaging information that will destroy Jonathan's life and must decide whether he will use it as it will also bring harm to Clark and Martha. Before he can decide what to do, Lex is shot and falls into a coma. He dreams that his mother visits him and shows him the life he could lead if he walks away from his father and LuthorCorp. In this alternate life, Lex is happily married to Lana with a baby on the way. Meanwhile, Chloe asks Clark to use his powers to deliver Christmas presents to needy kids.
Lana joins a sorority to get housing for her last-minute college registration, but the sisters have a deadly agenda which involves turning Lana into a vampire like themselves and sending her against Clark. Meanwhile, Chloe applies to become an intern at the Daily Planet and runs up against the editor-in-chief, Pauline Kahn.
Having been transported to the Fortress of Solitude, Clark is confronted by Jor-El, who tells him he cannot return to Smallville, instead he must stay and prepare to save the planet. Also, transported to the Fortress, Chloe is unable to handle the sub-zero temperature and collapses, begging Clark to use his powers to save her. Jor-El forbids him to leave, but finally acquiesces, telling Clark he must return before sunset or there will be dire consequences. Meanwhile, Lana is horrified when she sees two Kryptonian aliens emerge from a spaceship discovered in the remnants of the meteor shower. The two aliens destroy what's left of the town searching for Kal-El.