Almost 300,000 people die each year of heart failure (HF). The incidence of HF in the United States is 2.4%, and its prevalence is expected to jump by 46% by 2030; at that time, 1 in 33 Americans will have HF. This will impose a higher financial and health burden.  Thus, the management of HF has evolved significantly over the past few decades with the introduction of different pharmacological agents that improve mortality and reduce hospitalization. The American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) updated the HF guidelines for 2022 based on the available evidence over 40 years to mitigate that burden and improve survival. This state-of-the-art review aims to highlight the latest evidence regarding the pharmacological management of HF among all categories of HF based on ejection fraction. It focuses on the four medication pillars in HF and other beneficial medications. It emphasizes the recommended doses to achieve the maximal mortality benefit. The medications with some or no benefits or those with harmful effects in HF are also covered in this review.