The high replication rate of HIV, together with the low fidelity of its reverse transcriptase, provides the virus with an unprecedented genomic flexibility. This allows a fast adaptation to selective pressure, including antiviral drugs, resulting in the development of drug-resistant strains. The present improvements in the treatment of AIDS patients are at least partly owing to antiviral therapy. To assess the implications of HIV drug resistance on patient management, drug resistance assays for clinical HIV isolates are widely being used. Ideally, monitoring drug resistance should help clinicians in their treatment decisions. If patients would really benefit clinically from this strategy, then the gain from clinical improvement and from omitting drugs to which the virus is already resistant would outweigh the cost of drug resistance testing. In the next few years, researchers should consolidate the clinical benefit of antiviral drug resistance testing, and for this they need fast, reliable and cheap assays. All present assays are in vitro assays, which can only partly mimic the in vivo situation with confounding factors, such as cellular resistance (1). Efforts are presently made to establish in vivo assays (2; see also Chapter 10 ).