The rising numbers of new HIV infections among young people ages 15–24 in many developing countries, especially among young women, signal an urgent need to identify and respond programmatically to behaviors and situations that contribute to the spread of HIV and other sexually transmitted infections in early adolescence. Quantitative and qualitative studies of the sexual knowledge and practices of adolescents age 14 and younger reveal that substantial numbers of boys and girls in many countries engage in unprotected heterosexual vaginal intercourse––by choice or coercion––before their 15th birthdays. Early initiation into male–male or male–female oral and/or anal sex is also documented in some populations. Educational, health, and social programs must reach 10–14-year-olds as well as older adolescents with the information, skills, services, and supplies (condoms, contraceptives) they need to negotiate their own protection from unwanted and/or unsafe sexual practices and to respect the rights of others.