The series stars a college student living in Florida named "Mel". Mel lives with his pet cat and his roommate Leena.
What's Normal Anyway? contains examples of:
- Black Best Friend: Leena. While she has a brief storyline of her own when she meets a girl and goes off to France, she mainly exists to be Mel's best friend and voice of reason.
- Cloudcuckoolander: Mel is definitely not normal, but aside from being trans, he's also just kind of strange and in his own head a lot.
- Crossdresser: Not normally, but one comic has Mel dressing up in lipstick and an old dress of his because he wanted to get "get his money's worth" out of the dress.
- Everyone Calls Him "Barkeep": Beef. His given name is never revealed.
- Heteronormative Crusader: Mel and his friend Diego (who is also trans) get thrown out of a store by a homophobic owner who thinks they're a couple.
- Inopportune Voice Cracking: Mel's voice starts randomly cracking once he goes on hormones.
- In Touch with His Feminine Side: Mel is effeminate, partially due to his upbringing as female. Quite a sum of the comic deals with his issues concerning manhood and his lack of masculinity.
- Gag Haircut: In the prequel comic Mel gives himself a haircut in high school. It doesn't go well.
- Keet: Mel is very loud, energetic, and immature.
- Kindhearted Cat Lover: Mel is a sweet guy with a cat named Dr. Skateboard.
- Lovable Jock: Beef. He is very much a stereotypical straight bro in mannerisms and interests, but he is a nice guy and is supportive of Mel.
- Manchild: Mel tends to be one, which Leena occasionally points out.
- Slice of Life: The comic tells the life of a trans man as he goes through his transition.
- Sobriquet Sex Switch: Melissa -> Mel.
- Transgender: The comic stars a trans guy. His eventual boyfriend is also trans, and Mel is friends with a trans man named Diego.
- With Friends Like These...: The prequel focuses on Mel's friendship, and falling out, with his friend Carry after she has difficulty with Mel becoming more outwardly masculine.