Efter Metallo bryder ud og befrier Lillian Luthor, anholder politiet Lena Luthor, men Kara nægter at tro, at hendes ven er skyldig, og hun kæmper for at rense hendes navn.

Someone tries to kill Morgan Edge and he barely survives. He accuses Lena of being behind the attempt and vows to destroy her. When Lena fears her hatred for Morgan will take her to the Luthor dark side, Kara steps in to help her friend. Meanwhile, after Sam realizes she’s losing time, she confides in Alex who decides to run some medical tests to see if she can find out what’s going on with her new friend.

Secretly furloughed from prison due to failing health, Lex Luthor visits his sister, Lena, to seek her help finding a cure. Savvy as ever, Lena is suspicious of Lex's motives but when she's faced with a life and death situation, she must decide how she truly feels about her brother. Meanwhile, Supergirl and J'onn face off against Manchester Black. James' sister Kelly comes to town.

The subsequent complications from the Crisis leave Supergirl to face a chaotic threat.

Alex uses a pair of Obsidian contact lenses to visit a virtual National City where she takes on a whole new persona. Meanwhile, Kelly helps William investigate Lex. Kara deals with difficult news.

Supergirl and team race Nyxly for control of a magical totem that controls courage. Supergirl and Nyxly battle and each get a piece of the totem but learn the first person to pass the test of courage will gain control of the entire thing. Meanwhile, Lena is still struggling to make sense of her newfound gift.

Supergirl continues to fight Nyxly for the remaining totems but after Nyxly kidnaps William, Supergirl realizes she needs to take a more proactive stance to keep National City safe. Meanwhile, Alex faces the biggest challenge of her life.