The management of heart failure with reduced ejection fraction (HFrEF) has advanced in recent decades, and patients are surviving longer. The goals of HFrEF treatment are to reduce mortality, hospitalizations, and the severity of symptoms while improving functional status and quality of life. Treatments shown to reduce morbidity and mortality in patients with HFrEF, known as guideline-directed medical therapy, include renin-angiotensin system/neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. Guidelines recommend initiation with target dose titration within 6 to 12 weeks of diagnosis. Secondary therapies such as digoxin, hydralazine and isosorbide dinitrate, ivabradine, and vericiguat are indicated in certain patients with persistent or worsening symptoms. Guideline-directed medical therapy may require dosage adjustment due to adverse effects such as hypotension, hyperkalemia, and worsening kidney function. Intravenous iron replacement is recommended in patients with iron deficiency to improve functional status and quality of life. Device and interventional therapies may be indicated in those with prolonged QRS duration to decrease the risk of sudden cardiac death. Point-of-care ultrasonography can help diagnose heart failure and assess effectiveness of diuretic therapy.