The January issue has a number of exciting articles that cover a broad swath of cardiovascular pharmacology. One noteworthy contribution is an Emerging Concepts in Pharmacotherapeutics review article by Drs. Thomas D. Bernier and Leo F. Buckley, entitled Cardiac Myosin Activation for the Treatment of Systolic Heart Failure. Their article discusses at length two novel cardiac myotropes, omecamtiv mecarbil and danicamtiv. These drugs target cardiac myosin to increase left ventricular systolic performance by increasing the number of myosin-actin interactions. Neither affects cardiac myocyte calcium handling, which is thought to contribute to the life-threatening arrhythmias associated with cardiac calcitropes and calcium sensitizers. These agents also have minimal hemodynamic and renal effects. Phase 2 clinical trials have shown that these cardiac myosin activators prolong left ventricular systolic ejection time and promote left ventricular and atrial reverse remodeling. An ongoing phase 3 clinical trial, GALACTIC-HF, will determine the potential role of cardiac myosin activation in treating chronic heart failure with reduced ejection fraction. Additional analyses are needed to better understand the basis for myocardial ischemia and impaired diastolic function at higher plasma concentrations in some patients. However, overall, the evidence indicates that these agents offer promise for patients with advanced heart failure refractory to guideline-directed neurohormonal blockers.