In DSM-IV the occurrence of disturbed sleep is one of the principal diagnostic criteria for major depressive disorder (MDD). Further, there is evidence of reciprocity between the two conditions such that, even in the absence of current depressive symptoms, disturbed sleep often predicts their development. The present review discusses the effects of antidepressants on sleep and evaluates the use of the recently developed melatonin agonist-selective serotonin antagonists on sleep and depression. Although many antidepressants such as the tricyclics, monoamine oxidase inhibitors, serotonin-norepinephrine reuptake inhibitors, several serotonin receptor antagonists and selective serotonin reuptake inhibitors (SSRIs) have all been found successful in treating depression, their use is often associated with a disruptive effect on sleep. SSRIs, currently the most widely prescribed of the antidepressants, are well known for their instigation or exacerbation of insomnia. The recently introduced novel melatonin agonist and selective serotonin antagonist antidepressant, agomelatine, which has melatonin MT(1) and MT(2) receptor agonist and 5-HT(2c) antagonist properties, has been useful in treating patients with MDD. Its rapid onset of action and effectiveness in improving the mood of depressed patients has been attributed to its ability to improve sleep quality. These properties underline the use of melatonin analogues as a promising alternative for the treatment of depression.