NAD+ biology is involved in controlling redox balance, functioning as a coenzyme in numerous enzymatic reactions, and is a cofactor for Sirtuin enzymes and a substrate for multiple regulatory enzyme reactions within and outside the cell. At the same time, NAD+ levels are diminished with aging and are consumed during the development of inflammatory and autoimmune diseases linked to aberrant immune activation. Direct NAD+ augmentation via the NAD+ salvage and Priess-Handler pathways is being investigated as a putative therapeutic intervention to improve the healthspan in inflammation-linked diseases. In this review, we survey NAD+ biology and its pivotal roles in the regulation of immunity and inflammation. Furthermore, we discuss emerging studies evaluate NAD+ boosting in murine models and in human diseases, and we highlight areas of research that remain unresolved in understanding the mechanisms of action of these nutritional supplementation strategies.