Health worker shortages are a major bottleneck to scaling up antiretroviral therapy (ART), particularly in rural areas. In Lusikisiki, a rural area of South Africa with a population of 150,000 serviced by 1 hospital and 12 clinics, Médecins Sans Frontières has been supporting a program to deliver human immunodeficiency virus (HIV) services through decentralization to primary health care clinics, task shifting (including nurse-initiated as opposed to physician-initiated treatment), and community support. This approach has allowed for a rapid scale-up of treatment with satisfactory outcomes. Although the general approach in South Africa is to provide ART through hospitals-which seriously limits access for many people, if not the majority of people-1-year outcomes in Lusikisiki are comparable in the clinics and hospital. The greater proximity and acceptability of services at the clinic level has led to a faster enrollment of people into treatment and better retention of patients in treatment (2% vs. 19% lost to follow-up). In all, 2200 people were receiving ART in Lusikisiki in 2006, which represents 95% coverage. Maintaining quality and coverage will require increased resource input from the public sector and full acceptance of creative approaches to implementation, including task shifting and community involvement.