Transmitted resistance has become an important clinical problem in developed countries with long histories of antiretroviral use. In resource-limited settings, it is a foreseeable, if not insidiously emerging, issue. Any transmission route or currently approved antiretroviral drug may be involved. The clinical relevance of polymorphisms that commonly occur at sites known to be associated with resistance, and peculiarities of the non-B subtypes, are incompletely understood. Adverse clinical consequences that have been demonstrated with transmitted resistance include an increased risk of failing initial therapy and further development of resistance. Although treatment outcomes can be optimized by baseline resistance testing and virologic monitoring, these are impractical in most resource-limited settings at this time. The scale and impact of transmitted resistance can probably be reduced by comprehensive prevention and management strategies. Equally germane are epidemiological and clinical studies to extend understanding of the dynamics, clinical implications, and management of transmitted resistance.