In 2010, 3.5 million people were living with HIV in the World Health Organization Southeast Asia Region (SEAR), giving this region the greatest burden of HIV after Africa. Scale-up of antiretroviral therapy has resulted in over 717,000 benefitting from it by the end of 2010. A systematic review of studies of HIV drug resistance in the SEAR published between 2000 and 2011 was performed. Of 10 studies of transmitted HIV drug resistance in recently infected patients, all but two reported low levels (< 5%) of transmitted resistance. Of 23 studies of HIV drug resistance in pretreatment populations initiating antiretroviral therapy, three reported moderate levels (5-15%) of HIV drug resistance and 20 reported low levels. Amongst 17 studies of acquired HIV drug resistance, levels of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance ranged from 52 to 92% and 43 to 100%, respectively, amongst those with virological failure. Overall, data included in this review suggest that currently recommended first- and second-line regimens are appropriate for the cohorts studied. However, data were only available from two of 11 Southeast Asia Region countries and studies largely examined urban populations. Results are unlikely to be representative of the region. Studies lacked standardized methods, which greatly limits comparability of data and their use for public health and antiretroviral therapy program planning. Routine, standardized, and nationally representative HIV drug resistance surveillance should be strongly encouraged in the Southeast Asia Region countries to best characterize population-level HIV drug resistance. National-level HIV drug resistance surveillance data may be used to optimize delivery of HIV care and treatment and minimize emergence of population-level HIV drug resistance, thus promoting the long-term efficacy and durability of available first- and second-line antiretroviral therapy regimens.