The availability of highly active antiretroviral therapy (HAART), that suppresses replication of the human immunodeficiency virus type 1 (HIV-1), has dramatically improved the prognosis of HIV-infected patients. In populations with access to HAART, the course of the infection has changed from an inevitably fatal disease, characterized by a high incidence of opportunistic infections, into a potentially-treatable chronic condition. Unfortunately, HAART does not durably suppress HIV replication in 20-50% of treatment-naive patients and in up to 50-70% of treatment-experienced patients. In the majority of patients with viral rebound, drug-resistance-related mutations are detected. New infections through transmission of drug-resistant strains to individuals who have never been exposed to therapy are now being increasingly reported, despite all HIV prevention efforts. Moreover, recent reports correlate new infections by drug-resistant virus with suboptimal therapy response, which raises major public health concerns. Despite a large number of publications on the rate of primary resistance, it is very difficult to draw general conclusions. The large variation in methodology and interpretation illustrates the need for systematic approaches. Global surveillance is urgently warranted to monitor the circulating HIV-strains. In addition, follow-up research has to be performed to reveal the impact of drug resistance on future therapy options. This paper reviews current literature to elucidate the mechanisms, implications and magnitude of transmission of drug-resistant HIV-1.