This review focuses on the development of HLA-B*5701 genetic screening as a means of preventing drug hypersensitivity reactions caused by a commonly prescribed antiretroviral drug, abacavir. This strongly predictive genetic association, which in many respects represents a test case for the clinical application of pharmacogenetics, highlights the fine specificity of HLA-restricted immunity, here directed against a drug-specific antigen rather than an allogeneic molecule (as occurs in transplantation) or a pathogenic organism (as in viral infection). However, this example also demonstrates that successful implementation of pharmacogenetic screening requires that a range of criteria be adequately addressed. These include pharmaceutical factors (e.g. lack of alternative treatments with similar or improved cost effectiveness, safety, and efficacy), clinical factors (e.g. accurate diagnosis of the adverse event, in this case provided by clinical diagnostic criteria and adjunctive epicutaneous patch testing), sufficient objective evidence of the test's predictive value and generalizability (in this case provided by the first large-scale randomized trial of a pharmacogenetic test), as well as availability of quality-assured laboratory services that are responsive to the needs of targeted genetic screening. This example is intended to serve as a precedent for other pharmacogenetic screening strategies, particularly those aimed at reducing rates of serious drug hypersensitivity reactions in clinical practice.