The clinical indications for HIV drug resistance testing are discussed. The major limitations of using resistance testing in the clinical setting are the lack of evidence for a clinical benefit, the costs and the amount of knowledge required for a good interpretation of the results. In those situations in which these limitations can be overcome or are considered less important, resistance testing may be used today. For widespread clinical use, however, trials creating large databases and the design of expert systems translating the results for the use in individual patients will be required.