In this chapter we summarize the clinical differences found in the literature between men and women suffering from bipolar disorder. We include also mixed episodes which describe the simultaneous presence of manic and depressive symptoms in the same patient. This phenomenon is more prevalent in women. In men the manic component predominates, both at onset and throughout their lifetime. We consider also the major depressive episode with mixed symptoms, and risk of suicide in women with a diagnosis of bipolar disorder. Differences in comorbidity are discussed. Comorbidity with physical pathological conditions is more frequent in women while substance abuse is higher in men. Nevertheless, it is important to consider that women with bipolar disorder are at higher risk of drug and alcohol abuse than healthy population.