It is no exaggeration to say that, in the 30 years since antidepressants were introduced, they have revolutionised the management of depression, thus fulfilling, at least for depressive illness, Paracelsus' prophetic wish. We now have a group of drugs which can induce remission in a disease which is disabling and not infrequently fatal. Despite intensive research, however, our understanding of the mechanism of action of these drugs is still largely hypothetical. Even our methods of evaluation are sufficient only to enable one to decide whether an antidepressant drug is effective or ineffective; there is no experimental method which can rank them in an overall order of potency, and perhaps this should not be the aim, since there must be subgroups of depressed patients who will respond differently to any one agent.