OBJECTIVES The objective of the study was to explore variation in costs of ARTs between low- and middle-income countries, lines of therapy, and drug regimens over time. METHODS A search of database of WHO, Global Price Reporting Mechanism (GPRM), Pubmed and relevant grey literature from 2004-2008 was undertaken. Two reviewers selected all descriptive or interventional studies involving cost associated with ART therapy in low- or middle-income countries (as defined by World Bank criteria) and compared it. RESULTS Approximately 3,000,000 people are currently receiving ART in low-and middle-income countries. However, global coverage of ART is still limited, reaching 31% of the 9.7 million people in need at the end of 2007. In 2007, the weighted median price of the four most widely used combinations in first-line treatment was US$188/person/year. The median price paid for first-line treatment in low-income countries in 2007 ranged from US$92/person/year for the fixed dose combination (FDC) of stavudine + lamivudine + nevirapine to US$294 for the FDC of zidovudine + lamivudine + efavirenz, whereas this price ranged from US$91 to US$357 for respective FDC's for middle-income countries. The median cost of a regimen of didanosine + abacavir + ritonavir-boosted lopinavir, the most commonly used second-line regimen was US$ 1214 in low-income countries and US$ 3306 in middle income countries. In low and middle-income countries, the prices of most first-line treatments decreased by 30–64% from 2004 to 2007 whereas, the average prices paid for second-line regimens remained high. CONCLUSIONS Cost associated with ART is comparatively lower in low-income countries as compared to middle-income countries for first-line as well as second-line treatment regimens. Costs of most first-line treatments have decreased over time but coverage of ART still remains low in these countries.