The serendipitous discovery of the precursors of two of the major contemporary antidepressant families during the late 1950s, iproniazid for the monoamine oxidase inhibitors (MAOIs) and imipramine for the tricyclic antidepressants (TCAs), has guided the subsequent development of antidepressant compounds with predominantly serotonergic, noradrenergic or combined serotonergic and noradrenergic activity. Unfortunately, however, many depressed patients continue to remain symptomatic despite adequate treatment with pharmacologic agents currently available. When one reviews the list of pharmacologic agents currently approved for the treatment of Major Depressive Disorder (MDD), it is apparent that relatively few treatments with dopaminergic activity have been developed to date. Therefore, developing effective antidepressant treatments with pro-dopaminergic properties which also possess a relatively wide safety margin may further improve the standard of care for depression. In the present article we will briefly review studies focusing on the role of dopamine in depression followed by a comprehensive review of pharmacotherapies for depression with pro-dopaminergic activity.