Rollout of antiretroviral therapy (ART) in resource-limited countries has been identified as a global public health priority. Human immunodeficiency virus (HIV) treatment in the industrialised world is routinely accompanied by regular virological monitoring. By contrast, the implementation of ART in resource-limited settings requires use of standard first- and second-line therapy. One major consequence is the likely emergence of high-level resistance during first-line therapy since most people will stay on a virologically failing regimen for longer periods, potentially compromising the efficacy of second-line therapy. The evidence regarding resistance to triple-drug ART relates to the time at which virological failure occurs in populations from developed countries, with little data from resource-poor contexts where monitoring strategies, HIV subtypes and drug combinations are likely to differ.