Adverse reactions to medication are common. Some are predictable side-effects of the drug, others involve individual sensitivity to the drug. Allergic reactions are an important subset of these, but other specific sensitivities are caused by variations in the metabolism or mode of action of the drug. Patients who have experienced adverse reactions to medication will often refer to themselves as being allergic to the drug, regardless of the actual mechanism that caused the reaction. Consequently, anyone taking a history of ‘drug allergy’ needs to keep an open mind about the mechanism that may have been involved. Fortunately, most idiosyncratic reactions are minor, but some are severe, or even life-threatening. In most situations, there are satisfactory alternatives for the drug in question, but sometimes it is necessary to investigate and get an accurate diagnosis. The over-riding priority is to distinguish anaphylactic, potentially life-threatening reactions from other types of drug reaction, which are generally more protracted, less dangerous and usually managed by simple avoidance. While all doctors need to understand the underlying principles, drug challenges should only be undertaken by clinicians experienced in this area.