That's the boy Shuichi Nitori on the left, cross-dressing as a girl, with the girl Yoshino Takatsuki in boy's clothes on the right.
The manga story begins with Nitori and Takatsuki in grade school. They already felt the urge to cross-dress back then and became friends. Nitori was attracted to Takatsuki, but Takatsuki couldn't return his romantic feelings. The anime begins with the pair in junior high, where they are now surrounded by friends and classmates with their own issues, problems and strengths.
Nitori's friend Mako also sometimes cross-dresses as a girl; Chiba is a perpetually angry girl who is attracted to Nitori and jealous of his attraction to Takatsuki; Sarashina, a tall and outgoing girl, accepts everyone as they are.
There's not much external action in Hourou Musuko; it's more about the protagonists coming to terms with themselves and experiencing new realizations. As life in middle school progresses, underneath lies a poignancy: soon their bodies will be changing, something neither Nitori nor Takatsuki can do anything about. At one point Nitori and Mako dress up as girls and record their voices - their unbroken boys' voices - for posterity, as one day their boy child voices will be lost forever. Similarly, Takatsuki is angered when the school coach tells her to start wearing a bra; she tells Nitori that she envies his flat chest. But she soon gives in and starts wearing one.
Nitori and Takatsuki are both young enough - pre-puberty age - that it's conceivable that their desires aren't permanent, that this is a stage they will grow out of. It may be a stage born out of unconsciously wanting to avoid the responsibilities that are usually associated with being a certain sex - not wanting the baggage that comes with being male or being female. (They're too young to understand that both genders have their baggage and expectations - you can't escape it by simply wanting to be the other gender.) But it's equally conceivable that these desires are real and each will be faced with tough decisions in their teen years and beyond. When Chiba asks Nitori if he would have a sex change operation, Nitori says that he doesn't know.
Takatsuki looks better able to handle these complications. She has her transsexual friend Yuki (born a male, who transitioned to being female) to look to as a mentor, and she's more capable of dealing with strong emotions and feelings. Nitori seems genuinely fragile. One fears for him: pain seems unavoidable for him in the future.
But then, pain is a part of everyone's life, and some of that pain is related to being your true self in the face of opposition. Part of Hourou Musuko's message may be that what Nitori and Takatsuki face is on some level what all of us face: being ourselves no matter what others think. In that case, we can only wish Nitori and Takatsuki ganbare and hope they stay true to who they really are - whoever that may turn out to be.
