The coexistence of depression and anxiety is a common occurrence that frequently poses diagnostic and treatment challenges in the clinical setting. As epidemiological studies continue to confirm the enormous prevalence of this comorbid condition, the separation in diagnosis and treatment between depression and anxiety has become increasingly less pronounced. Additionally, the discovery that pharmacotherapeutic modalities have a broader range of efficacy, often overlapping both depression and anxiety, has led to an evolving reclassification of treatment, away from 'antidepressants' and 'anxiolytics' toward one based on mechanism of action. A rational approach to the systematized management of the various comorbidities of depressive and anxiety disorders is discussed.