Bipolar disorder is a heterogeneous condition with myriad clinical manifestations and many comorbidities leading to severe disabilities in the biopsychosocial realm. The objective of this review article was to underline recent advances in knowledge regarding the neurobiology of bipolar disorder. A further aim was to draw attention to new therapeutic targets in the treatment of bipolar disorder. To accomplish these goals, an electronic search was undertaken of the PubMed database in August 2015 of literature published during the last 10 years on the pathophysiology of bipolar disorder. A wide-ranging evaluation of the existing work was done with search terms such as "mood disorders and biology," "bipolar disorder and HPA axis," "bipolar disorder and cytokines," "mood disorders and circadian rhythm," "bipolar disorder and oxidative stress," etc. This endeavor showed that bipolar disorder is a diverse condition sharing neurobiological mechanisms with major depressive disorder and psychotic spectrum disorders. There is convincing evidence of crosstalk between different biological systems that act in a deleterious manner causing expression of the disease in genetically predisposed individuals. Inflammatory mediators act in concert with oxidative stress to dysregulate hormonal, metabolic, and circadian homeostasis in precipitating and perpetuating the illness. Stress, whether biologically or psychologically mediated, is responsible for the initiation and progression of the diathesis. Bipolar spectrum disorders have a strong genetic component; severe life stresses acting through various paths cause the illness phenotype.