This report presents a comprehensive analysis of the reasons why girls and young women smoke, drink and use drugs, and what increases or lowers their risk of substance abuse. It demonstrates that certain key risk factors for substance abuse are unique to girls and young women and pose a greater threat to them than to boys and young men. This report reveals the need for a complete revamping of the Nations prevention efforts to: tailor programs to the unique motivations and vulnerabilities of girls; intervene earlier with all girls, before unhealthy attitudes, beliefs and behaviors set in; target all girls and young women going through key life transitions that increase their vulnerability to substance use; target girls known to be at particularly high risk, such as those who have suffered from sexual or physical abuse, are depressed, have eating disorders, or have parents or friends who abuse substances. It illustrates the many life pathways that can hike the risk of substance abuse among girls and young women, including incorrect knowledge and beliefs about substances, inattentive parents, substance-using friends, schools and communities that turn a blind eye, physicians who are not vigilant to early warning signs, and exposure to the entertainment media advertising which shower girls and young women with unhealthy and unrealistic messages about smoking, drinking and weight loss. Six appendixes contain survey methodology, survey instrument, focus groups methodology, descriptions of national surveys, select female-specific prevention programs, and select female-specific treatment programs. (Contains 593 references and 5 tables.) (GCP)