Objectives. The goal of this study was to identify differences between gay, lesbian, bisexual, and transgender (GLBT) homeless youths and their heterosexual counterparts in terms of physical and mental health difficulties. Methods. A sample of 84 GLBT adolescents was matched in regard to age and self-reported gender with 84 heterosexual adolescents. The 2 samples were compared on a variety of psychosocial variables. Results. GLBT adolescents left home more frequently, were victimized more often, used highly addictive substances more frequently, had higher rates of psychopathology, and had more sexual partners than heterosexual adolescents. Conclusions. Homeless youths who identify themselves as members of sexual minority groups are at increased risk for negative outcomes. Recommendations for treatment programs and implications for public health are discussed.