Generalized anxiety disorder (GAD) is a relatively commun mental disorder in the general population, afflicting approximately 3% of community residents during their lifetime. It is not a benign condition, since significantly increased disability and dysfunction are found in GAD subjects compared to non-GAD subjects. For decades GAD has frequently been observed in the context of other mental and substance abuse disorders. Initially the weight of clinical opinion indicated that GAD was a residual disease which should only be diagnosed when other mental disorders are not present. More recently there has been a growing recognition that comorbidity is a fundamental characteristic of the course and nature of GAD. In a series of secondary analyses conducted in subjects in the National Comorbidity Study database, we found that 8 out of 10 subjects with lifetime GAD also had a comorbid mood disorder during their lifetime. We found unipolar disorders to be four times more common in GAD than bipolar disorders (67% vs. 17%), providing indirect support for the previously reported observation that GAD and major depression may share a common genetic diathesis. In addition, our analyses support the conclusion that when comorbid mood disorders are present in GAD, a significant increase in associated disability and dysfunction is also found. Thus this comorbid relationship has important implications for clinical course and outcome.