Anxiety and depressive disorders share many features, suggesting a common set of physiologic substrates. Recent research has indicated that mood can be categorized into 3 components by factor analysis: (1) somatic anxiety (a factor relatively specific to panic disorder), (2) anhedonic depression (which includes symptoms related to motivation and enjoyment and found to be specific to depression), and (3) general distress (a factor that cuts across all depressive and anxiety disorders studied). Antidepressant drugs, particularly serotonin reuptake inhibitors and serotonin receptor modulators, are effective for a wide variety of anxiety and depressive disorders. The impact on both anxiety and depression may be a result of an effect on a common set of physiologic targets relevant to the general distress dimension. At a cellular level, the antidepressants target components of the stress-adaptation system in brain, which may explain these common effects. On the other hand, there appear to be differences in the relative impact of serotonergic and noradrenergic drugs on the spectrum of distress and motivational symptoms. Basic research and clinical research suggest that serotonergic agents may be preferentially effective for symptoms of general distress, whereas catecholaminergic agents may target anhedonic depression symptoms.