Multiple funding sources provide research and program implementation organizations a broader base of funding and facilitate synergy, but also entail challenges that include varying stakeholder expectations, unaligned grant cycles, and highly variable reporting requirements. Strong governance and strategic planning are essential to ensure alignment of goals and agendas. Systems to track budgets and outputs, as well as procurement and human resources are required. A major goal of funders is to transition leadership and operations to local ownership. This article details successful approaches used by the newly independent nongovernmental organization, the Centre for Infectious Disease Research in Zambia.