Many findings that seem to be inconsistent in bipolar disorder research could be explained by heterogeneity of the illness and by imprecise diagnostic boundaries. This review of published data finds support for the existence of three main subtypes of bipolar disorder: (1) classical, (2) psychosis spectrum and (3) 'characterological'. These differ with respect to clinical presentation and course of illness, family history and possibly long-term treatment response. For instance, in a series of genetic studies, lithium responders showed an episodic course of illness with a family history of mostly bipolar disorder. In contrast, responders to lamotrigine monotherapy had a rapid-cycling clinical course and frequent comorbid conditions, especially in the anxiety-panic disorder spectrum. Their relatives had elevated rates of anxiety and major depression, but not bipolar disorder. In summary, recognising the clinical and familial subtypes of bipolar disorder might lead to more targeted treatment.