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- "How many times have you been there when I didn't know it, saving me?" – Lana Lang, Reckoning
Lana witnessed two aliens come out of the Black Ship and attack a cadre of police officers. She overheard them say that they were looking for "Kal-El". After Lex found her close to the site and took her back to the Luthor Mansion to recover, she saw Lionel Luthor in a trance, sketching strange symbols on the floor. Lionel told Lana that the Disciples of Zod must be stopped, and told her that meteor rock could destroy them. Lana went to the Smallville Medical Center, where the Kryptonians were laying siege and about to kill Lois Lane, and told them she knew where Kal-El was. She led them to the Luthor Mansion where they were exposed to the meteor rock in the secret vault, but they were able to escape. Before the aliens could kill Lana, Clark arrived and sent them into the Phantom Zone.
After Clark lost his powers for saving the ones he loved, he decided that he and Lana could have a real and honest relationship and finally start dating. During this time, Lana finally felt that Clark was totally open with her and the two lost their virginity to each other. However, their happiness did not last long due to the constant threats that Clark had to face.
Lana was shattered to learn that Clark had died after being seriously wounded by a man while trying to save Smallville, but when Clark came back safely to the farm, she was so glad that she didn't question how he managed to survive. However, because Clark regained his powers, their relationship was once more filled with secrets and lies, causing the things between the two to begin to change again.
Clark and Lana continued dating and then Lana enrolled into Metropolis University at the last minute, and was able to be inducted into the Ti-Psi sorority house. While she stayed there, she was transformed into a vampire meta human but was saved by Clark. Then Lana moved into Chloe's dorm room, as the Ti-Psi Sorority House was declared off-limits.
As Lana became obsessed with what happened during the last meteor shower, she started studying astronomy and meteors to try to discover the truth and came to the conclusion that there were possibly aliens living among them, much to the dismay of Clark. During this time, Lex supported Lana in her conclusions and helped her in her investigations. This caused Clark to obsess about the relationship between Lana and Lex to the point that he almost killed her, while being infected with silver Kryptonite, believing she had cheated on him.
Finally, Lex decided to enlist Lana's help in learning about the Black Ship, which he took from Lander's Field. Together, they would try to piece together the strange happenings in Smallville and the meteor showers that struck the town.
Although Lana understood Clark´s behavior with the help of Chloe, she noticed that Clark had returned to his old self and began to worry about what Clark was hiding. She felt especially worried given the fact that the two stopped having sex since he died and this caused a major rift in their relationship.
By that time, Lex's feelings towards Lana became increasingly apparent, but she remained loyal to Clark. It was clear that she knew that Lex had other intentions with her but especially after he risked his life protecting her while the two were being held hostage by two deranged Smallville deputies who wanted the Black Ship, Lana felt attracted to him because of the sincerity with which he treated her.
When Clark felt that he was losing Lana, he finally decided to tell her the truth about everything and showed her the Fortress of Solitude. Finally he proposed marriage to her and Lana accepted his proposal. After Jonathan Kent won the Senate race, Lana received a phone call from Lex and went to the Luthor Mansion to see how he was doing since he lost the election. After Lex saw her engagement ring, he figured that Lana knew about Clark's secrets and tried to force her to tell him, but she managed to get away. While driving away, Lana called Clark to warn him about Lex, but Lex was catching up to her. As she was trying to get away, a school bus collided with her car, killing her. Grief-stricken, Clark begged Jor-El to help him save Lana and was given a crystal to go back in time to prevent Lana's death. However, due to Clark's lies, Lana wanted a break from their relationship but after Jonathan Kent died of a heart attack, she backed off her idea and supported Clark by attending Jonathan's funeral.
Lana decided to try to make their relationship work again, and stood next to Clark to help him cope with the death of his father, including recovering Jonathan's watch that had been stolen from Martha. However, her relationship placed on hold due to Clark's secrecy and Lana started feeling closer to Lex, who offered her a shoulder to unload her problems.
Sometime later, Lana had an outing with Clark, and their relationship seemed to be on the road to recovery until he was hypnotized by Simone. She was called to Clark's barn where she found him and Simone having an intimate moment and under Simone's control, Clark told Lana that he had found someone else. Hurt and disgusted, Lana went to Metropolis to stay at her Aunt Nell's. After Simone was killed and Clark regained his senses, Chloe told Lana that he had been hypnotized. When she went to discuss it with Clark, he lied to Lana and said that he did not love her anymore. Heartbroken, Lana turned to Lex for comfort and to confide in him.
To find comfort from loved ones, Lana turned to two medical students who had created the highly-addictive Limbo drug, which Lana used to communicate with her parents in the afterlife. Desperate to use more of it, Lana spent more than a thousand dollars an injection and even stealing from Lex to pay for another one: but was caught by him. Lana was eventually saved by Clark. After Clark returned to life, Lana decided that she would never do anything like that again and she managed to get help and get off of drugs.
Lana then continued to work with Lex in their investigations about the Black Ship as a way to occupy her mind and during these days the attraction between the two became more evident. After an argument with Chloe for saying that something was happening between her and Lex, Lana goes to the Luthor Mansion to talk with Lex and avoid misunderstandings, but was astonished when Lex kisses her and then very confused, she kissed him back.
Some time later, Lana started dating Lex without telling Clark, who finds out when he walked in on Lana and Lex kissing. She told Clark later after Lex was attacked by Graham Garrett, because she wanted them to be honest with each other even if they weren't together anymore.
Finally, Lex had decided to let Lana in on a project of his that he was working with Milton Fine on. He told her that he created a vaccine that would make anyone immune to any of the world's powerful viruses, and showed Lana pictures of Fine and the Black Ship, which Fine was in one at one second, and the next second he was gone. Thinking that Fine was an alien like the Disciples of Zod, Lana told Lex that the "meteor rocks" were what they were vulnerable to. Once she returned to her dormitory at Metropolis University, she found Clark looking through her photographs of the Black Ship. Clark had Lana tell him where Lex and the lab were, if she didn't want anything bad to happen to Lex.
After Lex was rescued by Clark, Lana witnessed the Black Ship abduct Lex, and Fine appeared behind her, telling her that Lex is being prepared. She went to the Daily Planet where she told Chloe what happened, who later relayed the information to Clark. Later on, Lana overheard Clark saying that he might have to kill Lex. Lex later returned with Kryptonian powers, and showed them to Lana. He told her to meet him at the top of LuthorCorp.
Clark arrived at the Luthor Mansion, to ask where Lex was, and Lana demanded that Clark explain what was happening to Lex. Clark tried to get off the subject, and Lana, angry that he wasn't trusting her, stormed out after saying she didn't know how she could have ever loved him. When the electrical systems were all failing across the world due to Brainiac unleashing a powerful computer virus, Lana managed to get into the LuthorCorp building, and saw Lex, who was now possessed by General Zod, standing there. She told him that she was going to stand at his side, and the two shared a passionate kiss.