This article describes a family-based HIV prevention and mental health promotion program specifically designed to meet the needs of perinatally-infected preadolescents and their families. This project represents one of the first attempts to involve perinatally HIV-infected youth in HIV prevention efforts while simultaneously addressing their mental health and health care needs. The program, entitled CHAMP+ (Collaborative HIV Prevention and Adolescent Mental Health Project-Plus), focuses on: (1) the impact of HIV on the family; (2) loss and stigma associated with HIV disease; (3) HIV knowledge and understanding of health and medication protocols; (4) family communication about puberty, sexuality and HIV; (5) social support and decision making related to disclosure; and (6) parental supervision and monitoring related to sexual possibility situations, sexual risk taking behavior and management of youth health and medication. Findings from a preliminary evaluation of CHAMP+ with six families are presented along with a discussion of challenges related to feasibility and implementation within a primary health care setting for perinatally infected youth.