Drugs are among the main triggers of anaphylaxis, but identification of the culprit drug is frequently difficult. To confirm diagnosis of the causative agent, medical records and clinical history are fundamental. There are a few in vitro tests available in clinical practice, such as serum-specific IgE and basophil activation test. Skin tests are often useful for the diagnosis, although drug challenge is indicated in patients with inconclusive clinical history or to provide safe alternatives. Treatment of anaphylaxis is standard and intramuscular epinephrine is the main agent to prevent morbidity and mortality. Rapid desensitization may be indicated in selected cases.