SARIs (serotonin antagonists and reuptake inhibitors; nefazodone, trazodone) are new antidepressants with an interesting pharmacological profile. These antidepressant agents differ chemically and pharmacologically from selective serotonin-reuptake inhibitors (SSRI), monoamine oxidase inhibitors, and tricyclic antidepressants (TCA). Nefazodone and trazodone are active in a number of preclinical tests for antidepressant activity, and show high clinical efficacy in the treatment of depression with a more favorable side-effect profile than classic drugs such TCA. SARI have mechanisms of action distinct from other antidepressive agents. These compounds are potent antagonists of 5-HT2 receptors and inhibit serotonin transporter. Nefazodone blocks also norepinephrine transporter. SARI appeared effective in patients with major depression with efficacy similar to that of SSRI and TCA. SARI have been also reported to improve depression related insomnia, anxiety and many other secondary symptoms. This paper presents a review of pharmacological, pharmacokinetic and clinical profile of SARI. At the end, it is concluded that these agents present an interesting alternative for classical antidepressant drugs.