Antidepressants, a widely used group of drugs, are associated with a range of idiosyncratic reactions affecting in particular the liver, skin and both the hematological and central nervous systems. These reactions seem to be mediated by chemically reactive metabolites formed by the cytochrome P450 enzyme system, the toxicity occurring either directly or indirectly via an immune mechanism. Individual susceptibility is determined by factors, both genetic and environmental, which result in inadequate detoxication of the chemically reactive metabolite. Prevention of such reactions will depend on either the development of new compounds which are not converted to toxic metabolites or by prediction of individual susceptibility prior to drug administration.