Drug development in psychiatry has famously been something of a stop–start process. First, there were no truly effective psychotherapeutic agents, then, in the 1950s, phenothiazines, monoamine oxidase inhibitors and tricyclics all appeared in the space of a few years. Then, virtually nothing: no substantial developments for 25 years. In the mid–1980s the first selective serotonin reuptake inhibitors appeared, heralding a new era in psychopharmacology. Then, in 1990 clozapine was re-introduced, to be followed by other atypical antipsychotics and by drugs such as donepezil and acamprosate for entirely new indications. In addition, research into antidepressant therapy has produced new agents with varied modes of action and new strategies for the treatment of refractory depression.