The emergence of drug resistance in human immunodeficiency virus type 1 (HIV-1) may limit the clinical benefits of antiretroviral therapy. There is no objective evidence that the risk of drug resistance is greater in resource-limited settings than in the developed world. Treatment programmes will be most successful at preventing the spread of drug resistance if they provide healthcare infrastructures to maximize the effectiveness of antiretroviral therapy through the use of potent and convenient combination regimens that achieve durable suppression of HIV-1 replication.