Major Depressive Disorder (MDD) remains one of the current major sources of disabilities worldwide, accounting for considerable occupational, social, as well as cognitive, dysfunctions independent of depressive symptoms. Conventional management approaches focusing on reducing depressive symptoms have few benefits in managing disabilities in such patients. The chapter reviews current mental health approaches for managing disabilities in MDD, with emphasis on the major conceptual divide that exists between symptomatic and functional restoration. The chapter analyses the complexities associated with managing disabilities in MDD, which exist in terms of cognitive, psychosocial, as well as occupational, disabilities, besides neurobiological and environmental issues. Current evidence-based approaches in mental health, such as medication, psychological interventions, psychosocial interventions, online platforms for mental health delivery, and community-based interventions, are critically analyzed for their benefits in managing disabilities. Holistic approaches toward comprehensive healthcare delivery programs based on benefits associated with outcome measures for depression, focusing more on benefits associated with social rehabilitation, are explained. The chapter concludes with new approaches for managing disabilities in depression.