NAD plays an essential role in a number of biological processes. A study in this issue of Cell Metabolism (Revollo et al., 2007b) demonstrates that nicotinamide phosphoribosyltransferase (Nampt), also known as PBEF or visfatin, is a secreted enzyme and a source of systemic NAD. The authors show that Nampt-mediated NAD synthesis is necessary for beta cell function, providing fresh insights into the pathophysiology of metabolic diseases.