Drug hypersensitivity, including allergic reactions, is one of the side effects of drugs and is a daily worry for the clinician. They can be classified as immediate or non-immediate according to the time interval between last drug administration and onset. Immediate reactions occur within one hour and are manifested by urticaria, angioedema, bronchospasm, and anaphylactic shock. Non-immediate reactions occur after more than one hour and are manifested by maculopapular eruption, urticaria and serum sickness. Clinical and immunological studies suggest that type I (IgE-mediated) and type-IV (cell-mediated) pathogenic mechanisms are involved in most immediate and non-immediate reactions, respectively. New diagnostic tools, such as the basophil activation test and the lymphocyte activation test, have been developed and are under validation. When properly performed in specialised centres, a firm diagnosis is often possible and safe alternative medication can be proposed. In diagnosis, the patient`s history is fundamental; the allergologic examination includes in vivo and in vitro tests selected on the basis of the clinical features. Determination of specific IgE levels is still the most common in vitro method for diagnosing immediate reactions. The clinical tools allowing a definite diagnosis are few in number and include the following procedures: a thorough clinical history, standardised skin tests, reliable biological tests and drug provocation tests. All of these tools, although not always validated or predictive at the individual level and sometimes dangerous, have been carefully evaluated by the European Network of Drug Allergy (the European Academy of Allergy and Clinical Immunology drug hypersensitivity group of interest).