Objective: Early recognition of individuals at risk for depressive and anxiety disorders is key in influencing onset and course of these disorders. Parental history is a potent risk factor for the development of these disorders in offspring. However, knowledge about the magnitude of this risk is limited as largescale longitudinal studies with a follow-up into adulthood are scarce. Those offspring at highest risk may possibly be identified by easy-to-determine parental psychiatric characteristics, family context, and offspring characteristics. Methods: From 2000-2002, we recruited 523 offspring (age 13-25 years) of 366 patients who had received specialized treatment for depressive and/or anxiety disorder. Offspring DSM-IV mood (major depressive disorder, dysthymia, and bipolar disorder) and anxiety disorders (generalized anxiety disorder, social phobia, panic disorder, and agoraphobia) were assessed at baseline and at 4-, 6-, 8-, and 10-year follow-up. Results: Kaplan-Meier analysis showed that the cumulative incidence of mood and/or anxiety disorder was 38.0% at age 20 years and 64.7% at age 35 years. Parental early disorder onset (hazard ratio [HR] = 1.33; 95% CI, 1.00-1.77), having 2 affected parents (HR = 1.58; 95% CI, 1.10-2.27), and offspring female gender (HR = 2.34; 95% CI, 1.74-3.15) were independent predictors of offspring mood and/or anxiety disorder. Balanced family functioning (HR = 0.73; 95% CI, 0.56-0.96) was found to be protective against offspring risk. Conclusions: Offspring of depressed and anxious patients are at very high risk of a mood and/or anxiety disorder themselves. Parental early onset, having 2 affected parents, female gender, and family functioning are important additional markers that can be used in clinical practice to identify those offspring at greatest risk.