From the Center for Substance Abuse Prevention, the fourth monograph in the series “Points of Prevention,” discusses the issues of substance use and abuse, risk, protection, and gender. Data from the National Cross-Site Evaluation of High Risk Youth Programs study suggests gender differences in substance use and prevention. Following a comprehensive presentation of charts and graphs depicting gender differences in alcohol, tobacco, and marijuana use, this report argues that boys and girls respond to substance abuse prevention programs differently. While boys experience significant reductions in substance use following the completion of a substance abuse program, the benefits of such programs arise later for girls. This study further agues that female-only substance abuse programs are no more effective in reducing the rates of substance abuse than are mixed-gender programs and that girls report higher degrees of parental supervision than do boys. Figures, references