The increasing prevalence and incidence of diabetes and its long-term complications in sub-Saharan Africa (SSA) could have devastating human and economic toll if the trends remain unabated in the future. Approximately 90% or majority of patients with diabetes belongs to the adult onset, type 2 diabetes category while 10% have type 1 diabetes in SSA. However, because of the paucity of metabolic and clinical data, a clear understanding of the natural history of both diseases and the classification of diabetes subtypes has been hampered. Nevertheless, we have attempted to provide a concise review of the pathophysiology of both type 1 and type 2 diabetes as well as phenotypic and clinical variations in patients residing in SSA. The limited metabolic data, (albeit increasing), from high-risk and diabetic individuals in the SSA, have contributed significantly to the understanding of the pathogenetic mechanisms of diabetes and the variations in the presentation of the disease. Sub-Saharan African patients with type 1 diabetes have essentially absolute insulin deficiency. In addition, patients with type 2 diabetes in SSA region also manifest severe insulin deficiency with varying degrees of insulin resistance. Although the exact genetic markers of both diseases are unknown, we believe studies in patients of SSA origin who reside in diverse geographic environments (African diaspora) could potentially contribute to our understanding of the genetic and environmental mediators of both diseases. However, many intrinsic, individual and societal obstacles such as poor education and illiteracy, low socio-economic status and lack of access to health care make uncertain the translation of diabetes research in SSA. In this regard, effective management and/or prevention of diabetes in SSA individuals should adopt multidisciplinary approaches. Finally, innovative health care delivery and educational models will be needed to manage diabetes and its long-term complications in SSA.