The application of regenerative medicine (RM) in the clinic has gained significant momentum in countries of the Global North. In contrast, in the Global South, countries like South Africa have struggled to develop and integrate regenerative technologies within mainstream medicine. This is, in part, due to South Africa’s unique quadruple burden of disease, which presents significant challenges to a healthcare system already under strain, as well as the alarming disparity in equitable access to therapeutic interventions, exacerbated by persistent socioeconomic factors. Translating RM research outcomes to clinical practice is further limited by insufficient supportive infrastructure, scarcity of designated research funds, and lack of adequate human healthcare resources. This has consequences not only for advancing healthcare in African countries but also in countries with more developed economies, advanced healthcare systems, and established regulatory frameworks. These consequences occur because a complete understanding of clinical responsiveness to developing therapies can only be achieved when armed with knowledge generated from studies that included populations rich in biological diversity, and many of these populations are found in the Global South. The current chapter highlights key challenges facing the development and clinical translation of RM approaches in South Africa, emphasizing how the lack of data from diverse populations during the development of regenerative modalities in the clinic has negative consequences not only with regard to clinical outcomes on a local level but also on a global scale.