Nicotinamide adenine dinucleotide (NAD⁺) is a coenzyme found in all living cells. It serves both as a critical coenzyme for enzymes that fuel reduction-oxidation reactions, carrying electrons from one reaction to another, and as a cosubstrate for other enzymes such as the sirtuins and poly(adenosine diphosphate–ribose) polymerases. Cellular NAD⁺ concentrations change during aging, and modulation of NAD⁺ usage or production can prolong both health span and life span. Here we review factors that regulate NAD⁺ and discuss how supplementation with NAD⁺ precursors may represent a new therapeutic opportunity for aging and its associated disorders, particularly neurodegenerative diseases.