This paper is designed to call more attention to young people within the groups considered “most at risk” for HIV—those who sell sex, those who inject drugs, and young men who have sex with men. Despite the growing attention that has been given to programming for these groups, little explicit focus has emerged onthe particular needs of young people in these populations. Efforts to prevent HIV among young people have tended to focus on the general population of young people, for whom more is known about effective programming, instead of focusing on young people in most-at-risk groups. Research has begun to show the importance of focusing on young people within most-at-risk populations, and there are increasing examples of programmatic approaches for meeting their needs. But many challenges remain, including the fact that there are significant differences among young people between the ages of 10 and 24.