Medical and device therapy for heart failure (HF) has evolved substantially over the past decade. This has changed the landscape not only towards improved survival and quality of life for all HF patients but also resulted in more appropriate and efficient utilization of advanced HF therapies, including heart transplantation and mechanical support in those with end-stage HF. This chapter provides a comprehensive guide to navigating the evolving therapeutic options for HF patients, focusing on the four pillars of guideline-directed medical therapy for heart failure with reduced ejection fraction. The chapter also explores device therapies and highlights the need for patient-centered care.