Early adolescence remains an overlooked window of opportunity for public health intervention with girls and boys in sub-Saharan Africa. Minimal health data exist on pubescent girls and boys. Considerable morbidity and mortality related to HIV, sexually transmitted infections, and pregnancy emerge soon after puberty, suggesting the importance of targeting early adolescents. The fundamental goal of primary prevention would be better served if girls and boys between the ages of 10 and 14 years were targeted for effective and contextually relevant interventions. Such interventions should address healthy transitions to young adulthood to effectively advance the public health agenda with postpubescent (aged 15 to 24 years) young women and men. The global health community is overdue to build the empirical database for intervention with this age group.