This special supplement to Ethnicity & Disease presents the background and rationale, methodology, feasibility, and results of 4 separate interventions that were pilot-tested in Phase 1 of the Girls health Enrichment Multi-site Studies (GEMS) research program. The ultimate aim of the interventions was to prevent obesity in African-American girls. Four field centers, a Coordinating Center, and the National Heart, Lung, and Blood Institute were involved in a unique collaboration to generate and share ideas related to recruitment, formative assessment, and the standardization of some aspects of data collection while each field center designed and implemented a different intervention. Outcomes for recruitment, participation, and behavioral change were generally very favorable, particularly for the two field centers that have progressed to test their interventions in full-scale randomized trials in GEMS Phase 2. The intervention development and pilot study phase also provided many lessons about the importance of trust, openness, and community acceptability in implementing undertakings of this type. Given the paucity of evidence for effective strategies to prevent obesity overall and in high-risk populations, GEMS is an important step forward in developing well-grounded strategies for improving nutrition, physical activity, and weight status in African-American girls.