Major depressive disorder (MDD) is a prevalent and highly debilitating illness that causes significant functional impairment in many patients. Conventional pharmacotherapy, such as monoaminergic antidepressant agents, usually takes several weeks to improve symptomatology and has some adverse side effects, and in many cases, patients show clinical non-response. This has resulted in a quest to identify novel means of targeting the illness. Ketamine, a glutamate N-methyl-D-aspartate receptor antagonist, has been widely researched as an alternative intervention. Originally developed as an anesthetic, ketamine has been shown to exert an antidepressant effect at subanesthetic doses. A single dose of ketamine has been shown to have a rapid effect in resolving serious depressive symptoms including suicidal ideation with antidepressant effects. However, further research is needed as, in longer-term use, ketamine has the potential to be abused and certain psychological side effects, including psychotomimetic or dissociative effects, must be considered. This review highlights some of the benefits and risks of the use of ketamine in the treatment of MDD.