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This paper explores how indigenous R&D could be managed to unlock the full potential of health-based indigenous knowledge systems. The growing demand for biological or genetic resources for use in biotechnology and pharmaceuticals, as well as their commercialization, is a potentially viable option for sustainable development and public health equity. Studies show that IKS beneficiation could reduce poverty and generate wealth within the knowledge holding communities and their nations at large. The ‘knowledge’ has earned scientific validation and legitimacy by forming the basis of biomedical research and pharmacognosy, but IKS research has largely been inappropriate, Eurocentric and culturally irrelevant. Coordinated research on IKS would not only mainstream and develop the epistemology; it would indeed lead to product development and diversification of our factor-driven economies. As a novel area of research it should develop its indigenous methodologies and involve the knowledge holders as participants. WHO has not only resolved to promote the role of traditional medicines in health systems, it has also developed a strategy to provide regulatory guidance and quality assurance standards. Since biodiversity is arguably Africa’s most valuable asset, home-grown research, informing innovation that exploits indigenous knowledge potential should be intensified. This work has implications for policy and practice.