Testing for HIV resistance to antiretroviral drugs is a useful tool for guiding antiretroviral therapy. When combined with a detailed drug history and efforts in maximizing drug adherence, these assays might maximize the benefits of antiretroviral therapy. Studies of treatment-experienced patients have reported strong associations between the presence of drug resistance, identified by genotyping or phenotyping resistance assays, and failure of the antiretroviral treatment regimen to suppress HIV replication. Genotyping assays detect drug-resistance mutations that are present in the relevant viral genes (i.e., reverse transcriptase and protease). Certain genotyping assays involve sequencing of the entire reverse transcriptase and protease genes, whereas others use probes to detect selected mutations that are known to confer drug resistance. Genotyping assays can be performed rapidly, and results can be reported within 1–2 weeks of sample collection. Interpretation of test results requires knowledge of the mutations that are selected for by different antiretroviral drugs and of the potential for cross-resistance to other drugs conferred by certain mutations. Consultation with a specialist in HIV drug resistance is encouraged and can facilitate interpretation of genotypic test results.