Type 2 diabetes mellitus (T2DM) rates are three times higher in patients with bipolar disorder (BD), compared to the general population. This is a major contributing factor to the elevated risk of cardiovascular mortality, the leading cause of death in bipolar patients. There may be shared pathophysiology linking the two disorders, including hypothalamic-pituitary-adrenal and mitochondrial dysfunction, common genetic links, and epigenetic interactions. Life-style, phenomenology of bipolar symptoms, and adverse effects of pharmacotherapy may be contributing factors. Patients with BD and T2DM have a more severe course of illness and are more refractory to treatment. Control of their diabetes is poorer when compared to diabetics without BD, and an existing disparity in medical care may be partly responsible. Glucose abnormalities in bipolar patients need to be screened for and treated. Metformin appears to have the best benefit/risk ratio, and the dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists and analogues also appear promising, although these agents have not been specifically studied in populations with mood disorders. Physicians need to be aware of the increased risk for T2DM and cardiovascular disease in bipolar patients, and appropriate prevention, screening, case finding, and treatment is recommended.