Community health centers in the United States, first launched as a federal initiative in 1965, were rooted in models from South Africa, the American civil rights struggle, and a national commitment to address poverty. The first 2 centers, one serving a rural population in the Mississippi Delta and another a public housing project in Boston, incorporated such core principles as provision of primary care to a defined area or population; public health interventions addressing social determinants of health; emphasis on community participation; community empowerment leading to control of the new institutions; epidemiologic methods to identify problems and guide decisions; new combinations of clinical and public health personnel; and reduction of disparities in health and healthcare of the poor and minorities. The continuing relevance of these principles in today's greatly expanded health center network is reviewed.