In order to address the social, physical and economic determinants of urban health, researchers, public health practitioners, and community members have turned to more comprehensive and participatory approaches to research and interventions. One such approach, community-based participatory research (CBPR) in public health, has received considerable attention over the past decade, and numerous publications have described theoretical underpinnings, values, principles and practice. Issues related to the long-term sustainability of partnerships and activities have received limited attention. The purpose of this article is to examine the experiences and lessons learned from three Urban Research Centers (URCs) in Detroit, New York City, and Seattle, which were initially established in 1995 with core support from the Centers for Disease Control and Prevention (CDC). The experience of these Centers after core funding ceased in 2003 provides a case study to identify the challenges and facilitating factors for sustaining partnerships. We examine three broad dimensions of CBPR partnerships that we consider important for sustainability: (1) sustaining relationships and commitments among the partners involved; (2) sustaining the knowledge, capacity and values generated from the partnership; and (3) sustaining funding, staff, programs, policy changes and the partnership itself. We discuss the challenges faced by the URCs in sustaining these dimensions and the strategies used to overcome these challenges. Based on these experiences, we offer recommendations for: strategies that partnerships may find useful in sustaining their CBPR efforts; ways in which a Center mechanism can be useful for promoting sustainability; and considerations for funders of CBPR to increase sustainability.