Rare diseases (RD) constitute a real health problem in Africa and pose serious challenges in terms of both diagnoses. The whole continent faces a prevalence of several rare genetic diseases, and as genetic testing expands with technological advancements, the counts of population-specific diseases and mutation distributions are expected to rise. Their distribution across the African populations could be the result of the complex combinations of historical, socio-cultural, environmental, and economic factors. In this review, we examined published data on genetic rare diseases in Africa, reported on some of them that are the most prevalent, and focused on the implementation of precision medicine for the benefit of the African patients. It is imperative to incorporate genetic findings to ensure that appropriate diagnostic testing is available to Africans, providing all patients with the best information for diagnosis, treatment, genetic counselling, and reproductive decisions. This approach could pave the way for the successful implementation of precision medicine across the entire continent, offering a personalised public health strategy informed by evidence-based research in policy and drug development.