The naturalistic course of major depressive disorder (mdd) and risk indicators for recurrence and chronicity of mdd are best investigated using a psychiatric epidemiological population study without clear selection bias. However, such studies are scarce, thereby limiting clinical decision-making concerning the monitoring and maintenance of treatment.<br/> AIM: To present findings from the Netherlands Mental Health Survey and Incidence Study-2 (nemesis-2) regarding the recurrence and chronicity of mdd and associated risk indicators in the general population.<br/> METHOD: At baseline, two groups were selected to examine the recurrence and chronicity of mdd at follow-up. Diagnoses were assessed with the Composite International Diagnostic Interview (cidi) 3.0.<br/> RESULTS: Among respondents with remitted mdd (n = 746), the cumulative recurrence rate was 4.3% at 5 years, 13.4% at 10 years, and 27.1% at 20 years. Time to recurrence was predicted by vulnerability characteristics (childhood abuse, negative life events, parental psychopathology), physical health, functioning, clinical characteristics of depression (previous episodes, severity, medication use), psychiatric comorbidity and mental health use. Among respondents with current mdd (n = 242), 12% developed a chronic depressive episode over 6 years. The chronic course was predicted by risk indicators similar to those for recurrence, except for vulnerability characteristics and physical health.<br/> CONCLUSION: These risk indicators may help identify depressive patients requiring monitoring and who might benefit from preventive interventions or maintenance treatment.