The episode opens with a couple being told that their newborn baby has ambiguous gender and both male and female DNA. We then see a young teen boy collapse during a basketball game, and the team gets a new case. The parents are scared it is due to the gender issues at his birth (a blind uterus), but when an MRI rules that out, things get more complicated. The team quickly gets frustrated trying to diagnose and interact with the boy because the parents are too afraid to address the gender issue with him, and have kept it a secret all his life. 13 finds out that the boy's mother has strictly enforced gender stereotypes by forbidding him from taking dance classes and instead making him do sports like basketball or hockey. She empathizes much more with the boy than with the parents, and gives him just enough information to force the parents to be honest with their son.
Meanwhile, House is behaving unusually and when he passes out in his office, Cuddy and Wilson begin to suspect he is using heroin. Foreman and 13 are still seeing each other, but pretending they've broken up. The fact that Kutner and Taub have figured them out but House hasn't is a red flag for Foreman and he joins in suspecting that House is using illegal narcotics. What's really happening is very dangerous but also very effective, and they have to decide how to address the situation professionally.
Many aspects of this episode are emotional and dramatic, causing some people to feel that the series was continuing toward a more soap-opera format. However, I think this is a solid episode addressing a gender issue in a new way. (And I also feel that by season 5, if the show had stuck with a strict medical detective format, most fans would be quite bored with it. They're there for the characters and relationships, not just the mystery, right?) And sure, there was an episode in previous seasons which dealt with a beautiful female model having male DNA, but this is a very different approach to gender and something that is rarely explored in fiction. The previous episode didn't explore the gender construct at all, it ended with the reveal that the girl had internal testicles. There was no follow-up on the way the girl felt about her gender or how her father dealt with the news. This episode is about gender from the beginning, not just landing a surprise 'you're a boy!' at the end.
What makes it compelling is the the parents, who know about their son's gender complications but have kept it hidden from him, and are overly sensitive to any potential gender issue because of it. They enforce gender rules more than most parents, ever concerned that they made the 'wrong choice' when he was born. They create far more distress in him by scrutinizing his every interest, making him believe that just because he wants to take dance, he's not a 'real boy'. It's an important thing to give attention to for a lot of reasons, and there's a good message behind the episode - even if your kid doesn't know there's something different about them (and even if there ISN'T anything unusual about them), they'll feel like a freak if you treat them like one.