This chapter provides a comprehensive overview of the clinical approach to Major Depressive Disorder (MDD), with a focus on screening, diagnosis, management, monitoring, and prevention. It emphasizes the use of validated tools such as the PHQ-9 for early recognition and diagnosis. Management strategies are individualized based on symptom severity, with psychotherapy recommended as the first-line treatment for mild depression, and pharmacotherapy added for moderate to severe cases. The chapter details first-line antidepressants for both adolescents and adults, including their side effect profiles and guidelines for long-term monitoring. It also explores preventive strategies such as lifestyle modifications and psychoeducation to reduce recurrence and improve patient outcomes. Overall, this chapter serves as a practical guide for clinicians managing MDD in clinical settings.