Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is a protein with several suggested functions. Although the first discovery of this molecule as a pre-B-cell colony-enhancing factor suggested primarily a cytokine function, its rediscovery as the key enzyme in nicotinamide adenine dinucleotide generation has considerably widened its potential biological activities. Although originally thought to be produced in adipose tissue (i.e., adipocytes and infiltrating macrophages), its production seems to involve other cells and tissues such as skeletal muscle, liver, immune cells, cardiomyocytes, and the brain. Visfatin/NAMPT has both intracellular and extracellular effects influencing several signaling pathways. Its broad spectrum of effects is mirrored by its potential involvement in a wide range of disorders including human immunodeficiency virus infection, septicemia, myocardial failure, atherosclerosis, metabolic disorders, inflammatory diseases, malignancies, and neurodegenerative disorders and aging. Moreover, studies on visfatin/NAMPT in atherosclerotic disorders suggest a rather complex role of this molecule in pathophysiology, potentially mediating both adaptive and maladaptive responses.