Research designed to examine the relationship between creativity and mental illnesses must confront multiple challenges. What is the optimal sample to study? How should creativity be defined? What is the most appropriate comparison group? Only a limited number of studies have examined highly creative individuals using personal interviews and a noncreative comparison group. The majority of these have examined writers. The preponderance of the evidence suggests that in these creative individuals the rate of mood disorder is high, and that both bipolar disorder and unipolar depression are quite common. Clinicians who treat creative individuals with mood disorders must also confront a variety of challenges, including the fear that treatment may diminish creativity. In the case of bipolar disorder, however, it is likely that reducing severe manic episodes may actually enhance creativity in many individuals.