Objectives: Girls' rates of drug use have met up with and, in some instances, surpassed boys' rates. Although girls and boys share risk and protective factors associated with drug use, girls also have gender-specific risks. Interventions to prevent girls' drug use must be tailored to address the dynamics of female adolescence. Methods: One such intervention, called RealTeen, is a 9-session, web-based drug abuse prevention program designed to address such gender-specific risk factors associated with young girls' drug use as depressed mood, low self-esteem, and high levels of perceived stress as well as general drug use risk factors of peer and social influences. Web-based delivery enables girls to interact with the program at their own pace and in a location of their choosing. Implications: This article describes the processes and challenges associated with developing and programming a gender-specific, web-based intervention to prevent drug use among adolescent girls.