Multidrug-resistant organisms/bacteria (MDROs) have significant health implications that either have not been addressed or received only limited attention, especially in resource-constrained settings such as Africa, where access to newer, often costly antibiotics is limited. Acquisition of MDROs has been linked with poorer clinical outcomes and prolonged hospitalization. The evolution and spread of MDROs is influenced by factors such as selective pressure exerted by indiscriminate use of antimicrobials in both agriculture and medicine, lack of prescribing skills and training, lack of access to rapid and reliable diagnostics, suboptimal surveillance, as well as poor implementation and adherence to prevention measures. Reports indicate increased occurrence of MDROs in Africa, including members of Enterobacteriaceae which are often implicated in bloodstream, urinary tract, abdomen, skin and soft tissue infections. However, serious data limitation and underreporting are major hurdles that continue to hinder our understanding of the impact of antimicrobial resistance. In this review, we sought to address this gap by providing up-to-date data on the epidemiology of MDROs across the continent, including data on their prevalence and current detection and prevention methods.