One of the consequences of massive investment in antiretroviral access and other AIDS programmes has been the rapid emergence of large numbers of lay workers in the health systems of developing countries. In South Africa, government estimates are 65,000, mostly HIV/TB care-related lay workers contribute their labour in the public health sector, outnumbering the main front-line primary health care providers and professional nurses. The phenomenon has grown organically and incrementally, playing a wide variety of care-giving, support and advocacy roles. Using South Africa as a case, this paper discusses the different forms, traditions and contradictory orientations taken by lay health work and the system-wide effects of a large lay worker presence. As pressures to regularise and formalize the status of lay health workers grow, important questions are raised as to their place in health systems, and more broadly what they represent as a new intermediary layer between state and citizen. It argues for a research agenda that seeks to better characterise types of lay involvement in the health system, particularly in an era of antiretroviral therapy, and which takes a wider perspective on the meanings of this recent re-emergence of an old concept in health systems heavily affected by HIV/AIDS.