Provocation tests are regarded as the “gold standard” to establish or exclude the presence of hypersensitivity to a certain drugs because they reproduce not only allergy symptoms but other adverse manifestations, irrespective of their pathomechanism. Provocation testing is potentially harmful and should be considered only after balancing the risk-benefit ratio in the individual patient. The reasons for false-positive and false-negative results are numerous, including loss of sensitization, cofactors not being included in the diagnostic procedure, and the potential induction of tolerance during provocation. When conducted by experienced clinicians in a carefully monitored setting, however, drug provocation testing is a safe method to confirm or exclude drug hypersensitivity.