Due to the potential hazards of drug allergies, an early and reliable diagnosis is crucial. The use of in vivo tests is not recent but, because of the hazards of skin testing in patients with a history of anaphylaxis, they had been abandoned for a while. Recent reevaluations have shown that for some drugs, e.g. antibiotics-reliable skin tests can ensure the diagnosis of drug allergy in up to 70% of cases. Many in vitro tests based on well-defined mechanisms, e.g. the basophil degranulation test have been used for the diagnosis of totally unrelated allergic mechanisms. It is almost impossible to interpret their validity as diagnosis tools. Nevertheless, other tests, e.g. the lymphocyte transformation test which have been evaluated in well-conducted recent studies, seem to have a good predictive value. Their use is still restricted to clinical trials or research studies. A reliable clinical approach as well as a detailed examination of the drug intake remains obligatory to diagnose drug allergy. Available in vivo and in vitro tests are sometimes used to confirm the diagnosis. The sensitivity and specificity of these tests is evaluated in clinical studies. Research to improve the existing tests and to develop new diagnostic tools is still of paramount importance.