Intracoronary adenylyl cyclase 6 (AC6) gene transfer in patients with heart failure safely increased left ventricular function beyond standard heart failure therapy, found a randomized, placebo-controlled, phase 2 clinical trial. Preclinical studies had previously shown benefits of increased AC6 on cardiac myocytes and the heart. Novel therapies are urgently needed for a disease that has seen little improvement in hospitalization rates and mortality in the past decade, despite advances in drug and device therapy (Hammond HK et al. JAMA Cardiol. doi:10.1001/jamacardio.2016.0008 [published online March 30, 2016]).