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HIV/AIDS is catastrophic both from a public health perspective and in terms of its impact on economic and social stability in many of the most severely affected nations, including virtually all of southern Africa. A public health response alone is insufficient to address this devastating epidemic. Political leadership at the highest levels is needed to mobilize a multisectoral response to the impact of HIV/AIDS on educational systems, industry, agriculture, the military, and other sectors. With a few notable exceptions, political response was slow to mobilize in the early years of the epidemic, but response has dramatically improved in the past 18 months. The Joint United Nations Programme on HIV/AIDS (UNAIDS) is involved in ongoing efforts to encourage political leaders to make a multisectoral response to the epidemic a major focus of their national plans.