Adolescent chronic antisocial behavior is costly but concentrated in a relatively small number of individuals. The search for effective preventive interventions draws from empirical findings of three kinds of gene-by-environment interactions: (1) parenting behaviors mute the impact of genes; (2) genes alter the impact of traumatic environmental experiences such as physical abuse and peer social rejection; and (3) individuals and environments influence each other in a dynamic developmental cascade. Thus, environmental interventions that focus on high-risk youth may prove effective. The Fast Track intervention and randomized controlled trial are described. The intervention is a 10-year series of efforts to produce proximal change in parenting, peer relations, social cognition, and academic performance in order to lead to distal prevention of adolescent conduct disorder. Findings indicate that conduct disorder cases can be prevented, but only in the highest risk group of children. Implications for policy are discussed.