Nicotinamide adenine dinucleotide (NAD+) is identified as the major hydrogen acceptor in oxidation/reduction reactions, participating in energy metabolism and the signal transmission mediated by NAD+-dependent enzymes. Depletion of NAD+ is a key mechanism underlying the pathogenesis of various cardiovascular diseases such as cardiomyopathy, myocardial ischemia, cardiac hypertrophy, and heart failure. Elevating the level of NAD+ to regulate the function of the NAD+-dependent enzymes including Sirtuin family, PARP, and cADPR synthetases, and maintaining the balance of NAD+/NADH ratio, can effectively impede the progress of diverse cardiovascular diseases by reprogramming energy metabolism, repairing DNA damage, attenuating apoptosis, mitigating oxidative stress, and suppressing inflammation. Therefore, increasing the content of NAD+ exhibits great potential for treating an array of cardiovascular diseases.