Depression is an ancient illness. Rich descriptions of the clinical phenomenology of depression are found in the writings of the Greek physician, Hippocrates (460–377 B.C.), and the Roman physician, Galen (129–199 A.D.), as well as those of the Arabic physician, Ishaq Ibn Imran (tenth century A.D.), who anticipated the precipitating role of stress in depression. Independent of culture, the core construct of depression as a psychological disorder defined by despondency and a loss of will that symptomatically and behaviorally resembles grief or sadness has remained the same for over 2,000 years. However, in contrast to sadness or grief triggered by a loss, depression often has no identifiable triggering experience or if a triggering experience is identified, the depressive reaction is seemingly disproportionate to the loss. Our present day clinical definition of major depressive disorder (MDD) is defined by the presence of depressed mood and/or anhedonia accompanied by a combination of other symptoms including feelings of worthlessness or guilt, poor concentration or indecision, thoughts of death or suicidal ideation, fatigue, and changes in appetite and sleep that persist for at least for 2 weeks in the absence of an identifiable cause such as a medical disorder, reaction to a medication or illicit drug, or bereavement. In addition to MDD, a number of other psychiatric disorders also have depressive symptoms as a prominent feature and these include dysthymia, bipolar disorder, posttraumatic stress disorder, and various personality disorders.