Kara turns on her friends and the citizens of National City after being exposed to Red Kryptonite makes her malicious and dangerous. Also, Cat appears on THE TALK to discuss Supergirl.

Kara gains a new ally when the lightning-fast superhero The Flash suddenly appears from an alternate universe and helps Kara battle Siobhan, aka Silver Banshee, and Livewire in exchange for her help in finding a way to return him home.

Mxyzptlk returns with a proposition for Kara – what if she could go back in time and tell Lena her secret before Lex did, would things turn out different? Looking back over key moments throughout the series, Kara must decide if she wants to change history to become friends with Lena again.

The Monitor sends Harbinger to gather the worlds’ greatest heroes - Supergirl, The Flash, Green Arrow, Batwoman, White Canary, The Atom and Superman - in preparation for the impending Crisis. With their worlds in imminent danger, the superheroes suit up for battle while J’onn and Alex recruit Lena to help them find a way to save the people of Earth-38. This crossover continues on Batwoman S1E09, The Flash S6E09, Arrow S8E08, and Legends of Tomorrow S05E01.

When a new threat emerges in National City, Kara/Supergirl teams up with her cousin, Clark Kent/Superman, to stop it. Kara is thrilled to have family in town but it leaves Alex feeling a bit left out. Meanwhile, Hank and Supergirl are stunned by the pod that came crashing to Earth.

J'onn J'onzz reveals the details of meeting Kara and Alex's father, Dr. Jeremiah Danvers, and assuming Hank Henshaw's identity. Also, Kara debates trusting someone new with her secret identity and Siobhan plots against Kara.

CADMUS attacks National City with a Kryptonite-powered villain who ends up seriously hurting Supergirl. Superman blames Hank because the Kryptonite was stolen from the DEO. Meanwhile, Kara’s first day at her new job doesn’t go as planned after she meets her new boss, Snapper Carr.

Kara and her friends must rely on their inner strength and courage when an earthquake strikes National City. Also, Alex’s mistrust of Hank reaches a breaking point when the earthquake traps them in the DEO with Jemm, a powerful alien escapee.

Kara goes toe-to-toe with Astra when her aunt challenges Kara’s beliefs about her mother. Also, Cat is threatened with being removed as the CEO of CatCo after a hacker exposes her private and damaging emails.

Kara must help Hank face his painful past when a White Martian, a member of the alien race that wiped out his people, kidnaps Senator Miranda Crane, an anti-alien politician. Also, Cat's estranged son, Adam, arrives in National City.

Eliza comes to town to celebrate Thanksgiving with her daughters. Alex decides it’s time to come out to her mother; Kara is shocked when Eliza suggests Mon-El has feelings for her, and Winn and James consider telling Kara the truth about the Guardian. Meanwhile, Cadmus unleashes a virus that instantly kills any alien in the vicinity so Kara enlists an unexpected ally – Lena Luthor. The epic superhero crossover kicks off tonight when Barry Allen and Cisco Ramon seek Kara's help with an alien invasion on their Earth. The crossover continues on The Flash S03E08 Invasion! (II), Arrow S05E08 Invasion! (III) and DC's Legends of Tomorrow S02E07 Invasion! (IV).

As Alex searches for Jeremiah and Kara investigates a series of alien kidnappings, the sisters realize they must break the rules to foil a new Cadmus plot. In an effort to get Snapper Carr to run a story that would help her stop Cadmus, Kara agrees to set up an interview between Snapper and Supergirl.

Supergirl challenges Rhea to battle to save National City. Meanwhile, Superman returns and Cat Grant offers Supergirl some sage advice.

Kara’s friends must find a way to save her life when a parasitic alien attaches itself to her and traps her in a dream world where her family is alive and her home planet was never destroyed. Also, Alex, Hank and the DEO must fend off a Kryptonian attack while Kara is out of commission.

After Metallo breaks out of prison and frees Lillian Luthor, the police blame Lena for his escape and arrest her. Despite overwhelming evidence, Kara refuses to believe her friend is guilty and fights to clear Lena’s name. Flashbacks reveal how Lena came to be a Luthor.

Kara and Alex head home to Midvale for a little R&R. While there, Kara recalls a painful memory of a childhood friend's death and how that traumatic experience brought the Danver sisters closer together.

Supergirl is forced to do battle with an unexpected foe and must risk everything – including her life – to prevent Non and Indigo from destroying every person on the planet.

An attack is made on the President as hot-button, alien vs. human rights issues heat up in National City. Supergirl and the DEO are assigned to protect the President and bring in the responsible party. Alex teams up with Detective Maggie Sawyer to investigate the case while Kara searches for a recently escaped Mon-El, who she fears may be the alien behind the assault.

The Guardian debuts to lend a hand after a parasite alien drains Supergirl of her power. Mon-El considers a less than desirable new career which then leads him to contemplate his motives. Alex struggles with a new reality.

Supergirl grapples with whether or not to obey the President's orders regarding Rhea's latest actions. Meanwhile, Cat Grant returns to National City.

While a new villain is under arrest at the DEO, Supergirl uses him to try and understand who is responsible for the recent attacks. Meanwhile, Andrea and Lena think back on their tumultuous past.

Supergirl finally learns the truth about Lena while tangling with Leviathan. J'onn J'onn makes a discovery about his brother's whereabouts.

Supergirl realizes that in order to stop Lex and Leviathan she must work with the one person she never thought she’d trust again – Lena. Nia keeps dreaming about Brainy but struggles with what the dreams are trying to tell her. Meanwhile, Brainy realizes there is only one way to stop Lex.

Personal and professional stress get the better of Kara when she goes too far during a training exercise against Red Tornado, a military cyborg commissioned by Lucy Lane’s father, General Sam Lane. Also, Cat’s tough exterior is shaken by a visit from her judgmental mother, Katherine, and Alex enlists Winn to look into her father’s mysterious death.

With Astra in captivity at the DEO, her husband, Non, captures Hank, leading to a tense standoff between the two sides. Also, Kara continues to refute Cat's allegations that she is Supergirl.