Bipolar disorder is a severe psychiatric disease characterized by varying treatment response among individual patients. Effects of certain treatments, for instance, lithium, can be predicted from clinical characteristics of patients and their family histories. This led to a suggestion that a treatment response could identify subtypes of bipolar disorder particularly suited for gene-mapping studies. In this paper we review family and molecular studies of bipolar disorder responsive to lithium, as well as studies aiming to identify polymorphisms associated with the treatment response itself. While molecular genetic research and gene expression studies promise to bring new insights into the pathophysiology of the illness and the nature of treatment response, and thus provide new information for better treatment of bipolar disorder in the future, results from family studies and studies of clinical correlates of treatment response may already be utilized in the management of bipolar disorder.