Background: Comorbidity of depressive and anxiety disorders is common and remains incompletely comprehended. This paper summarizes findings from the Netherlands Study of Depression and Anxiety (NESDA) regarding prevalence, temporal sequence, course and longitudinal patterns; sociodemographic, vulnerability and neurobiological indicators; and functional, somatic and mental health indicators of comorbidity. Methods: Narrative synthesis of earlier NESDA based papers on comorbidity (n=76). Results: Comorbidity was the rule in over three-quarter of subjects with depressive and/or anxiety disorders, most often preceded by an anxiety disorder. Higher severity and chronicity characterized a poorer comorbidity course. Over time, transitions between depressive and anxiety disorders were common. Consistent comorbidity risk indicators in subjects with depressive and anxiety disorders were childhood trauma, neuroticism and early age of onset. Psychological vulnerabilities, such as trait avoidance tendencies, were more pronounced in comorbid than in single disorders. In general, there were few differences in biological markers and neuroimaging findings between persons with comorbid versus single disorders. Most functional, somatic, and other mental health indicators, ranging from disability to cardiovascular and psychiatric multimorbidity, were highest in comorbid disorders. Limitations: The observational design of NESDA limits causal inference. Attrition was higher in comorbid relative to single disorders. Conclusions: As compared to single disorders, persons with comorbid depressive and anxiety disorders were characterized by more psychosocial risk determinants, more somatic and other psychiatric morbidities, more functional impairments, and poorer outcome. These results justify specific attention for comorbidity of depressive and anxiety disorders, particularly in treatment settings.