Nicotinamide adenine dinucleotide (NAD+) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NAD+ is required for the activity of multifunctional enzymes including sirtuins and poly(ADP-ribose) polymerases (PARPs) that regulate post-translational modifications, DNA damage responses, and calcium signaling. Recent research indicates that NAD+ participates in a multitude of processes dysregulated in cardiovascular diseases. Therefore, supplementation of NAD+ precursors including nicotinamide riboside (NR) that boost or replete the NAD+ metabolome may be cardioprotective. This review examines the molecular physiology and preclinical data with respect to NAD+ precursors in heart failure related cardiac remodeling, ischemic/reperfusion injury, and arrhythmias. In addition, alternative NAD+ boosting-strategies and potential systemic effects of NAD+ supplementation with implications on cardiovascular health and disease are surveyed.