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Regional institutions increasingly shape economic and political development in Southern Africa. In this review, I discuss the historical background of this region and examine the major regional institutions that address key common concerns of economic development, trade, regional migration, and shared natural resources. I also discuss the challenges for, and to, regional integration, including competition among different regional organizations, poverty, war, political instability, and the developing HIV/AIDS pandemic. This research can be understood as illustrative of general research on regions. In particular, it shows how political leaders have created new sets of institutions to deal with important regional concerns, how regional institutions have affected economic development, and how the development of regional organizations is the outcome of regional politics as well as the interaction of national-level decisions.