As a result of the scale-up of antiretroviral treatment (ART) programmes and substantial financial support worldwide, an increasing number of HIV-infected individuals in low-income and middle-income countries (LIMCs) now have access to ART. Despite this progress, important questions remain on the best use of ART and how patients should be maintained on a successful regimen. This Review addresses some of the issues faced by those managing the epidemic in LMICs, including when to start treatment, choice of first-line ART, and when to switch regimens. Although the first priority must be continued expansion of access to ART, there should be a move towards starting ART earlier to treat individuals before they reach advanced stages of disease, to reduce early mortality, and to build support for improved monitoring of treatment failure. There is also a need for more randomised controlled studies to identify the long-term outcomes, cost-effectiveness of ART, and use of virological monitoring in LMICs.