Plasmodium vivax and Plasmodium falciparum are southern Africa’s most prevalent human malaria parasites. Although several control measures have been focused on lowering malaria incidence and fatalities in the region, as malaria diagnostics improve, there is more evidence that P.vivax and P.falciparum constitute significant health challenges in the region. Furthermore, P.vivax can lie dormant in the liver and is resistant to the combination treatment with artemisinin. It also infects Duffy-negative people who were thought to be immune to it. This review focuses on the prevalence of P.vivax and P.falciparum in southern Africa, examines the Duffy susceptibility to P.vivax and P.falciparum and reviews their epidemiology. In addition, challenges in malaria treatment, control and diagnostic approaches are discussed. This review concludes with the status of malaria eradication strategies and future malaria research areas.