This article reviews the novel atypical antidepressant drug agomelatine (Valdoxan), which is currently being actively investigated in the United States for the treatment of depression but is not yet approved by the U.S. Food and Drug Administration. Agomelatine is a synthetic analog of the hormone melatonin and has unique pharmacological properties that distinguish it from other currently available antidepressant drugs. Agomelatine is efficacious, safe, and well tolerated but does not appear to have major efficacy advantages compared with other antidepressant drugs. Because of its unique pharmacology and relatively benign tolerability profile, however, it may be a more effective alternative for patients who do not respond to or cannot tolerate currently available antidepressant drugs.