A strategic imperative in mood disorders is to identify innovative mechanisms that translate into improved therapeutics when compared to the extant options. More specifically, there is a need for treatments with greater efficacy, shorter time-to-peak efficacy, greater durability of effect as well as improved tolerability profiles. Moreover, priority has also shifted towards identifying mood disorder therapeutics capable of targeting domains of psychopathology that are most pervasive, debilitating and inadequately treated by conventional pharmacology (e.g., anhedonia, cognitive impairment). Available preclinical, translational, observational and clinical data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) hold promise as potentially mechanistically-informed therapeutics in persons with mood disorder. Although metabolic effectors are implicated as a putative mechanism of action of GLP-1RAs, non-mutually exclusive targets also include direct effects on neuroplasticity, neurogenesis, neurodifferentiation, neuroprotection, anti-apoptotic and autophagy mechanisms. Available evidence does support origination of adequate and well-controlled clinical studies in both major depressive disorder and bipolar disorder as acute and/or maintenance treatments. Although association with suicidality and GLP-1RAs have been reported, causality has not been established. Moreover, preliminary evidence suggests that GLP-1RAs may benefit aspects of mood disorder psychopathology (e.g., reward) that may be predictive of potential beneficial effects on aspects of suicidality.