Nefazodone is a fourth-generation antidepressant with novel serotonergic actions. It is a potent antagonist of synaptic 5-HT(2) receptors and a moderate blocker of synaptic 5-HT reuptake. Its mild synaptic blockade of norepinephrine is of little clinical importance. Besides its effectiveness in depression, nefazodone is effective in depression-related anxiety. Of all the antidepressants, nefazodone is least likely to induce sexual dysfunction. This drug increases sleep efficiency and reduces the number of nighttime awakenings. Nefazodone, compared with many other antidepressants, is unlikely to induce a withdrawal syndrome if abruptly stopped.