Transmitted drug resistance is an emerging phenomenon with important clinical and public health implications. It has been reported in 3.4% to 26% of HIV-infected persons in the USA. Most cases affect non-nucleoside reverse transcriptase inhibitors or nucleos(t)ide reverse transcriptase inhibitors. Transmitted protease inhibitor or multi-class resistance is uncommon, occurring in <5% of cases. The genital tract may function as a reservoir of transmissible drug-resistant variants or a site for low-level viral replication at a time plasma HIV is suppressed. Transmitted drug-resistant HIV variants, including those that exist in very low titers (minority populations), are associated with suboptimal virologic response to initial antiretroviral therapy. Baseline resistance testing, preferably genotype, appears to be cost-effective and is recommended for all treatment-naïve patients in the USA, although prospective trials have not been performed. It appears transmitted drug resistance is still relatively low in developing countries, but there is a dearth of information.