Heart failure with reduced ejection fraction is a significant driver of morbidity and mortality. There are common misconceptions regarding the disease processes underlying heart failure and best practices for therapy. The terms heart failure with reduced ejection fraction and left ventricular systolic dysfunction are not interchangeable terms. Key therapies for heart failure with reduced ejection fraction target the underlying disease processes, not the left ventricular ejection fraction alone. The absence of congestion does not rule out heart failure. Patients with cardiac amyloidosis can also present with heart failure with reduced ejection fraction. A rise in serum creatinine in acute heart failure exacerbation is not associated with tubular injury. Guideline directed medical therapy should be continued during acute exacerbations of heart failure with reduced ejection fraction and should be started in the same hospitalization in new diagnoses. Marginal blood pressure is not a relative contraindication to optimal guideline directed medical therapy. Guideline directed medical therapy should be continued even if ejection fraction improves. There are other therapies that provide significant benefit besides the four key medications in guideline directed medical therapy.