This review synthesizes recent advances in understanding SIRT1-mediated cardioprotection across a spectrum of heart diseases, including myocardial ischemia/reperfusion (I/R) injury, heart failure (HF), diabetic cardiomyopathy (DCM), cardiac hypertrophy, aging-related cardiac dysfunction and circadian rhythm disruption. This evidence concerns the gene SIRT1 and familial dilated cardiomyopathy.