Heart failure with reduced ejection fraction (HFrEF) represents at least half of the cases of heart failure, which is a syndrome defined as the inability of the heart to supply the body's tissues with an adequate amount of blood under conditions of normal cardiac filling pressure. HFrEF is responsible for high costs and rates of mortality, morbidity, and hospital admissions, mainly in developed countries. Thus, the need for better diagnostic methods and therapeutic approaches and consequently better outcomes is clear. In this article, we review the principal aspects of pathophysiology and diagnosis of HFrEF, with focus on emerging biomarkers and on recent echocardiographic methods for the assessment of left ventricular function. Furthermore, we discuss several major developments in pharmacological and nonpharmacological treatment of HFrEF in the last years, including cardiac resynchronization therapy, implantable cardioverter defibrillators, and the recent and promising drug LCZ696, focusing on current indications, unanswered questions, and other relevant aspects.