While the contribution of agriculture to GDP is relatively small for Southern Africa, approximately 70% of the population in this region relies upon agriculture. The dependence on primarily rain-fed agriculture in the context of climate change creates daunting challenges for policymakers, leaders and citizens moving forward. Regional trade agreements, like the African Continental Free Trade Agreement, have the potential to greatly expand agricultural trade for Africa. However, to ensure that increased trade benefits the populations dependent upon agriculture, policies and programmes will need to be designed with a recognition of three important issues: 1) the persistence of food insecurity and smallholders, 2) insecure land tenure rights amidst the financialization of agriculture lands and 3) gender inequality. Compounding these issues is the broader context of a region that has among the highest rates of HIV/AIDS cases in the world and extreme income and wealth inequality. These issues will shape the transformative potential of agriculture in Southern Africa.