Family and twin studies attest to the importance of genetic factors influencing susceptibility to bipolar disorder and to its genetic and phenotypic complexity. Although linkage and candidate gene association studies have repeatedly implicated some chromosome regions and certain genes, they have not produced the level of unambiguous support required to confirm the involvement of any specific gene or sequence variant in the pathogenesis of bipolar disorder. However, strong associations have recently been reported in meta-analyses of genome-wide association studies and the systematic study of structural variation is ongoing. These findings indicate that the study of large, phenotypically well-characterized samples will make an important contribution to delineating the etiology and pathogenesis of bipolar disorder and thereby pave the way for major improvements in clinical management.