BACKGROUND: HIV prevention organizations are increasingly adopting more intensive and evidence-based strategies with the goal of protecting targeted populations from HIV infection or transmission. Thus, capacity building has moved to the forefront as a set of activities necessary to enable HIV prevention organizations to plan, implement, monitor, and evaluate prevention programs and services. Cost-effective approaches to the provision of capacity building assistance traditionally use strategies that compromise efficaciousness and more intensive approaches can be cost prohibitive. In addition, traditional approaches treat program planning and implementation and program monitoring and evaluation as two separate entities, even though they are interdependent aspects of an efficient and effective service delivery system. OBJECTIVE: This article describes a framework for building sustainable organizational capacity that combines high- and low-intensity approaches; integrates program planning, monitoring, and evaluation; and focuses on building understanding of the value of appropriate organizational change. METHODS: The described framework was used over a 3-year period with 52 community-based organizations funded by the Centers for Disease Control and Prevention (CDC) and organizations funded by CDC-funded health departments. RESULTS AND CONCLUSIONS: The article includes lessons learned, recommendations for building long-term sustainability, organizational change at various levels, and the need to develop standardized indicators to measure changes in organizational capacity