Major depressive disorder (MDD), one of the mood disorders, is publicly well known as depression but rather serious alarming diseases that can be seen at almost every outpatient clinics and hospitals around the world recently. The exact cause of MDD is still not clearly understood but it has long been known to have considerable connection with hereditary modalities, neurotransmitter concentrations, neuroendocrine alterations, psychosocial factors, and surrounding environment. Also, MDD is inextricably linked to chronic underlying diseases, and has a strong association with increasing age and underlying mental disorders. This morbid phenomenon can be considered as a chronic mental illness with a high morbidity, demonstrating frequent remit and relapse of the condition even with and after supportive guidance, underlying disease management, determined drug, psychotherapy, and etc. Obviously, all forms of mood disorders are associated with sleep disturbance, but this review paper will only briefly review the etiology, physiology, diagnosis, clinical presentation, and treatment of MDD to avoid linguistic and informational redundancy. More specifically, this paper will review through studies how recent oral treatment with trazodone HCl is characteristic and differs from the other anti-depressive treatment in patients with MDD and insomnia in narrative manner.