In the context of a long-term institutional 'twinning' partnership initiated by Indiana and Moi Universities more than 22 years ago, a vibrant program of research has arisen and grown in size and stature. The history of the AMPATH (Academic Model Providing Access to Healthcare) Research Program is described, with its distinctive attention to Kenyan-North American equity, mutual benefit, policies that support research best practices, peer review within research working groups/cores, contributions to clinical care, use of healthcare informatics, development of research infrastructure and commitment to research workforce capacity. In the development and management of research within our partnership, we describe a number of significant challenges we have encountered that require ongoing attention, many of which are "good problems" occasioned by the program's success and growth. Finally, we assess the special value a partnership program like ours has created and end by affirming the importance of organizational diversity, solidarity of purpose, and resilience in the 'research enterprise.'