Bipolar disorder (BD) is associated with significant morbidity and mortality, partly due to its numerous clinical comorbidities. BD is linked to a wide range of medical conditions, including metabolic syndrome, cardiovascular diseases, chronic pain, and respiratory disorders, among others. These comorbidities often exacerbate the burden of the illness, leading to increased polypharmacy and reduced life expectancy. Moreover, pharmacotherapy, while essential for managing mood symptoms, can contribute to the development or worsening of certain comorbidities. Lithium, a cornerstone in BD treatment, is associated with renal and thyroid dysfunction, among other side effects. Anticonvulsants, another mainstay treatment, have their own set of adverse effects, including hepatic and cognitive complications. Clinical monitoring of BD patients should encompass thorough physical examination, laboratory investigations, and consideration of medication-related risks. A multidisciplinary approach and collaborative care model are paramount for optimizing outcomes and reducing the physical and mental burden of BD.