Proteomics is a biotechnology research area that is generally defined as the large-scale study of protein expression, structure and functions. Primarily, proteomics is used to study relative cellular, subcellular and extracellular abundances of proteins expressed at a defined physiological state on a large scale. In contrast to the analysis of mRNA expression studies, generally referred to as transcriptomics, proteomics approaches take into consideration the post-transcriptional, translational and post-translational modifications of polypeptides. Over the past 10 years, the proteomics field has been growing tremendously and contributing positively to biotechnology, particularly in North America, Europe and Asia. Research output in Africa is still very low in comparison. This article reviews proteomics capacity as well as research activities in South Africa. We highlight, with examples, the potential that this technology has in the acceleration of disease biomarker discovery and its role in drug design. Our ultimate objective is to promote further developments, research and applications of proteomics in South Africa, aiming for the generation of new scientific knowledge for our continent and for the rest of the world.