Major depressive disorder (MDD) represents a leading cause of disability. This study examines the course of disability in patients with chronic, recurrent and remitting MDD compared to healthy controls and identifies predictors of disability in remitting MDD. We included 914 participants from the Netherlands Study of Depression and Anxiety (NESDA). DSM-IV MDD and WHO DAS II disability were assessed at baseline and at 2, 4 and 6 years. Six-year total and domain-specific disability were analysed and compared in participants with chronic (n = 57), recurrent (n = 120), remitting (n = 127) MDD and in healthy controls (n = 430). Predictors of residual disability were identified using linear regression analysis. At baseline, most disability was found in chronic MDD, followed by recurrent MDD, remitting MDD and healthy controls. Across diagnostic groups, most disability was found in household activities, interpersonal functioning, participation in society and cognition. A chronic course was associated with chronic disability. Symptom remission was associated with a decrease in disability, but some disability remained. In remitting MDD, higher residual disability was predicted by older age, more severe avoidance symptoms, higher disability at baseline and late symptom remission. Severity of residual disability correlated with the severity of residual depressive symptoms. Symptomatic remission is a prerequisite for improvements in disability. However, disability persists despite symptom remission. Therefore, treatment of MDD should include an explicit focus on disability, especially on the more complex domains. To this end, treatments should promote behavioural activation and address subthreshold depressive symptoms in patients with remitted MDD.