Nicotinamide adenine dinucleotide (NAD⁺) is both a coenzyme for hydride-transfer enzymes and a substrate for NAD⁺-consuming enzymes, which include ADP-ribose transferases, poly(ADP-ribose) polymerases, cADP-ribose synthases and sirtuins. Recent results establish protective roles for NAD⁺ that might be applicable therapeutically to prevent neurodegenerative conditions and to fight Candida glabrata infection. In addition, the contribution that NAD⁺ metabolism makes to lifespan extension in model systems indicates that therapies to boost NAD⁺ might promote some of the beneficial effects of calorie restriction. Nicotinamide riboside, the recently discovered nucleoside precursor of NAD⁺ in eukaryotic systems, might have advantages as a therapy to elevate NAD⁺ without inhibiting sirtuins, which is associated with high-dose nicotinamide, or incurring the unpleasant side-effects of high-dose nicotinic acid.