Bipolar disorder (BD) is a disabling and chronic neuropsychiatric disorder that is typified by a complex illness presentation, episode recurrence and by its frequent association with psychiatric and medical comorbidities. Over the past decade, obesity has emerged as one of many comorbidities generating substantial concern in the BD population due to important prognostic implications. This comprehensive review details the bidirectional relationship between obesity and BD as evidenced by alterations in the structure and function of the central nervous system, in addition to greater depressive recurrence, cognitive dysfunction and risk of suicidality. Drawing on current research results, this article presents several putative mechanisms underlying the synergistic toxic effects and provides a framework for future treatment options for the obesity-BD comorbidity. There is a need for more large-scale prospective studies to investigate the bidirectional relationships between obesity and BD.