Various clinical issues are involved in the appropriate diagnosis and proper treatment interventions for patients with major depressive disorder (MDD). Despite a number of diverse antidepressants for treating MDD now, response and remission rates following adequate trials of antidepressant intervention are still not satisfactory. Furthermore, a significant proportion of MDD patients have residual symptoms, which are associated with increased relapse and recurrence of MDD, leading to negative impacts on the clinical course and outcomes of MDD. Timely and appropriate decision-making regarding the proper management of such cases is required in our routine daily practice. These issues are illustrated and also framed by one MDD case with a complicated clinical course. This review paper may give physicians clinical insight into how we can effectively and properly evaluate and manage such patients in clinical practice.