This article looks at the most important developments of antidepressants in the 1990s. The major properties of selective serotonin reuptake inhibitors, reversible and selective inhibitors of monoamine oxidase type A, selective serotonin and noradrenaline reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants are discussed. On the basis of the specific advantages and disadvantages of these compounds, unmet medical needs in the psychopharmacological treatment of depression are considered and the profile of an ideal antidepressant is outlined, followed by some closing remarks on potential new mechanisms of action. The most important progress in the past 10 years has been the development of compounds which possess markedly reduced binding capacities at receptor sites not linked to their antidepressive actions. This development has improved tolerability, both in therapeutic use and in overdose. Three main therapeutic needs have still to be met: (i) superior efficacy to tricyclic antidepressants; (ii) a faster onset of action; and (iii) reliable effectiveness in the treatment of therapy-resistant depression.