Close relatives of patients with manic and depressive episodes have been known to experience the same or similar psychiatric conditions. The familial nature of a trait, in general, does not necessarily imply its genetic basis; it was only through twin and adoption studies that bipolar disorder (BD) was shown convincingly to be heritable. At the same time, the estimated heritability of bipolar disorder between 70% and 80% suggests that a nonnegligible portion of the phenotypic variance is environmental, nongenetic in origin. In the last several decades, we have witnessed an intensive search for specific susceptibility genes and efforts to link these genes to the pathophysiological mechanisms of the illness. While still very incomplete, this search is yielding important clues. Last but not least, the familial aspects of the illness are useful in the clinical management of this severe psychiatric illness.