While school-based sex education is one of the key program and policy solutions to improve adolescent sexual health outcomes, new efforts are needed to strengthen its overall impact. The cognitive, hormonal, emotional, and physical changes that accompany the onset of puberty and occur throughout the teenage years play a significant role in aspects of adolescent sexual risk taking. Thus, one approach to advancing current understanding of these complex issues is to leverage emerging knowledge in developmental affective neuroscience over the past 15 years, which suggests some potentially promising innovations that may inform new educational directions to improve adolescent sexual health. Exploring the conceptual and empirical advances in understanding adolescent brain development through the lens of the conceptualization, implementation, and evaluation of sex education, this article provides new perspectives that encourage the testing of innovative approaches to sex education policy and practice.