Allergic drug reactions are a significant cause of morbidity and mortality. Because it is difficult to identify the culprit drug and the underlying pathophysiologic mechanisms involved in these reactions, a systematic approach should be adopted in the evaluation of drug-allergic patients. Initially, the type of reaction should be determined. It should be realized that not all adverse reactions are allergic in nature. Allergic drug reactions comprise only a small category of adverse reactions in general. Therefore, the physician must determine if the reaction demonstrates features common to immunologic reaction. Subsequently, a detailed history should be obtained and a physical should be performed. Important information includes medication usage, previous drug exposure, current illness, family history of drug allergy and personal history of drug allergy. In managing the drug-allergic patient, the physician may choose to: select an alternative, non-cross-reacting drug if future therapy is needed; premedicate prior to future drug exposure if such regimens have been shown to be effective; or consult an allergist regarding the potential graded challenge or desensitization.