In an ideal world, it would be simple and mutually rewarding for researchers in high-income countries (HICs) to collaborate with researchers in low-income countries (LICs) to conduct high-quality research to improve health outcomes. Surely, the abundance of intellectual, technical, and financial riches in HIC universities could be harnessed to the experience of "local" clinicians, using "local" here to reference those working in the context studied, to bring about productive and equitable partnerships that further the missions of both groups. In reality, however, it is inevitable that the needs of researchers in HICs and LICs sometimes diverge. Even when both groups are dedicated to improving the health of the most vulnerable, they are each embedded in systems that operate under different constraints and through different incentive structures. Here we outline some of these issues and offer our long-term approach as a jointly beneficial strategy to redress these challenges. For "local" implementers, the decision to conduct research is weighed against difficult trade-offs. Given limited personnel, facilities, and materials, research comes at short-term costs to patient care, and it is often difficult to predict the long-term value. Scarcity is not only a factor in prioritizing healthcare activities; relatively few LIC healthcare professionals have the opportunity for research training, and access to medical literature is limited by language, technology, and the cost of journal subscriptions. These barriers make it challenging for even the best-trained LIC researcher to effectively compete for funding. These issues mean that many partnerships are inherently unequal. Successful HIC researchers are highlytrained, have access to medical literature, and understand how to obtain grant funding. Relatively few face the tradeoffs and time constraints that LIC researchers encounter. This can result in HIC researchers setting the agenda of "collaborative" research, often choosing research questions that are fundable but less relevant to the local setting. HIC researchers face very different constraints. At most HIC universities, faculty need to bring in grant funds to finance their research. The majority of these applications are rejected. For example, in 2014 the NIAID set