The pathophysiology of bipolar disorder (BD) remains poorly understood. Current psychopharmacologic treatments are often poorly tolerated and carry high rates of treatment resistance. Mounting evidence has suggested that innate immune system dysfunction may play a role in the pathophysiology of BD. Elevated proinflammatory cytokine levels have been identified. The innate immune system is a novel therapeutic target in BD. Lithium has been shown to have antiinflammatory properties. Further research is needed to establish the role of antiinflammatory agents in the treatment of BD; however, evidence from several clinical trials indicates that antiinflammatory agents may be incorporated into clinical practice soon.