Although awareness on bipolar disorder has increased during the last decade, this condition remains characterized by a disabling burden, in terms of morbidity and functional impairment. This paper aims to review some critical issues in the current knowledge on Bipolar disorder. Although large European epidemiological studies are lacking, Bipolar disorder is characterized by a set of severe features, including an early age of onset, a chronic outcome and an important suicidal risk. A majority of bipolar patients also experience a comorbid Axis I condition, including substance abuse, anxiety disorder and attention-deficit hyperactivity disorder. This situation presents a therapeutic challenge, since antidepressants or methylphenidate may be associated with the risk of inducing mania. Recently, a large number of studies have provided evidence for the efficacy of new compounds in the treatment of both mania and bipolar depression, but also in long-term relapse prevention. Recent research has also allowed for the redefinition of the concept of mood stabilizer and for improving existing guidelines on the clinical management of Bipolar disorder.