Nicotinamide phosphoribosyltransferase (NAMPT; EC 2.4.2.12), was originally discovered as the cytokine pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin, and has several suggested functions. It was found to be an important cofactor for stem cell factor– and interleukin (IL)-7-mediated B cell maturation. However, in 2002 the murine homologue of PBEF was found, and this proved to be an enzyme catalyzing the reaction between nicotinamide and 5-phosphoribosyl-1-pyrophosphate yielding nicotinamide mononucleotide (NMN), an intermediate in the biosynthesis of NAD/NADH: central molecules involved in energy metabolism, reductive biosynthesis, and antioxidation, histone deacetylation, cell death, and intracellular calcium release. This widened its potential biological activities. Interestingly, both extracellular (cytokine-like) and intracellular (enzymatic) functions seem to be responsible for its relevance in immunity, metabolism, and stress responses in both physiology and pathophysiology.