Getting into anime means having your horizons broadened, learning about strange and new concepts like senpai and kohai (senior/junior in a school or organization), something that doesn't exist in English. It also means getting used to some gender-related surprises, thanks to the extensive Japanese tradition of stories involving males assuming female roles or vice-versa. Appreciating the comedy and/or drama of mixed-up gender roles goes back very far, to the kabuki plays of the Edo Period in which extremely talented male actors would fill female roles, or the Takarazuka Revue, the all-female troupe that's put on on a variety of shows with women expertly playing male roles since 1913. Anime is rife with stories that break gender rules, from the classic Rose of Versailles, which follows Lady Oscar, raised as a boy, throughout the events of the French Revolution, or the Rumiko Takahashi classic Ranma 1/2, about a boy cursed to change into a girl whenever he gets wet, usually with hilarious results. Even the dating-sim games we've been involved with have been known to bend a gender or two, such as the X-Change series. Perhaps the highest expression of the mixing-up of gender roles is Maria Holic, centered around a boy who dresses up as a girl to attend a prestigious Catholic school at the behest of an eccentric grandmother.
Maria Holic, the pinnacle of the Japanese tradition of gender-mashing.