Exercise limitation is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF), but it is not consistently improved by any of the current guideline-directed medical therapies. JAMA Deputy Editor Gregory Curfman, MD, discusses whether omecamtiv mecarbil can improve peak exercise capacity in patients with HFrEF with Gregory D. Lewis, MD, from Massachusetts General Hospital, and Mark H. Drazner, MD, MSc, from University of Texas Southwestern Medical Center.