NAD + has gone in and out of fashion within the scientific community a number of times since its discovery in the early 1900s. Over the last decade, NAD + has emerged as a potential target for combatting metabolic disturbances and the mitochondrial dysfunction that is mediated through sirtuin (SIRT) enzymes. The beneficial metabolic effects of the NAD + /SIRT axis have triggered an increased interest in NAD + as an enhancer of energy metabolism. As a result, a myriad of publications have focused on NAD + metabolism, with the majority of the work having been performed using in vitro models, and in vivo work largely consisting of interventions in Caenorhabditis elegans and rodents. Human intervention trials, on the other hand, are scarce. The aim of this review is to provide an overview of the state-of-the-art on influencing NAD + metabolism in humans and to set the stage for what the future of this exciting field may hold.