Tramadol (Ultram, Ultracet) is a centrally acting synthetic opioid with analgesic efficacy comparable to codeine. Antinociception is attributed to low but effective affinity for the mu-opioid receptor (μ), as well as reuptake inhibition of the monoamines norepinephrine (NE) and serotonin (5HT). Dual action antidepressants mirtazapine (Remeron), duloxetine (Cymbalta), and most notably venlafaxine (Effexor), which tramadol is closely related to in structure, also inhibit NE and 5HT reuptake. These medications are proven effective antidepressants and this shared monoaminergic action resulted in the research of tramadol as a potential treatment for depression. The present article intends to substantiate the use of tramadol in this manner by analyzing several decades of research which is presented as an illustration of neuronal theories, as well as lab work and case studies of both the supporting ideas and potential hazards. Finally, the article promotes the benefits of acute action in comparison to modern antidepressants and the documentation of low abuse rates while maintaining an object view of the risks, most notably, the risk for addiction from agonist action on μ-receptors.