The efficacy of 5-HT uptake inhibitors, including paroxetine, as antidepressants is compared with that of the reference tricyclic antidepressants. It is suggested that some of the older tricyclic antidepressants might not have been released for general clinical use if tested by today's rigorous standards. Placebo-controlled, multicentre studies indicate that 5-HT uptake inhibitors are both effective as antidepressants and well tolerated by depressed patients. They also appear to have a role in the treatment of depression when associated with personality disorders, in the treatment of obsessive-compulsive disorder and bulimia, and in resistant depression. Moreover, the evidence for efficacy in the prophylaxis of depression is better established for 5-HT uptake inhibitors than for reference antidepressants.