BACKGROUND: Middle and low-income countries have scaled up HIV treatment in the past 5 years. To maintain this effort, information regarding the amounts and types of drugs is needed. Shortages or overstock of active pharmaceutical ingredients make the scale-up efforts more difficult and costly. To inform global planning and implementation, we estimate the volume of current and future demand for active pharmaceutical ingredients for first and second-line antiretroviral drugs. METHODS: Using regression analysis and documented assumptions, we estimated the number of individuals receiving antiretroviral drugs to 2008. The volume of active pharmaceutical ingredients was calculated using two methods: a normative approach modelling implementation of country-specific guidelines, and an empirical model projecting current trends in drug use estimated by a survey of country HIV programmes. RESULTS: The number of patients treated was estimated to reach 3.38 million by the end of 2008, of which 94.6% would be on first-line and 5.4% on second-line treatment. The largest estimated absolute demand volumes for 2008 were for nevirapine, lamivudine, and zidovudine using either approach; the largest proportional increases in 2007-2008, were observed for emtricitabine, tenofovir, indinavir, and nelfinavir. The gap between normative and empirical estimates was greatest (most positive) for tenofovir, zidovudine, didanosine, and smallest (most negative) for saquinavir and nelfinavir. CONCLUSION: A comparison of the results from the normative and empirical demand quantities suggests that more tenofovir, zidovudine and didanosine would be required if national treatment guidelines were fully implemented, whereas the countries seem to be using more saquinavir and nelfinavir than would be required by their current guidelines.