Pre-B-cell colony-enhancing factor (PBEF) was recently found in high levels in visceral fat, and was therefore renamed visfatin. This new adipocytokine exerts insulin-mimetic effects in mice and in cultured cells by binding to and activating the insulin receptor. Despite some recent studies on this topic, the proposed role of visfatin in metabolism remains largely unknown. Initially, PBEF/visfatin was discovered as a cytokine for the differentiation of B-cells. Pre-B-cell colony-enhancing factor was also shown to inhibit apoptosis of neutrophils in sepsis and was discussed as a novel biomarker for acute lung injury (ALI). Although PBEF is missing a signal sequence, its secretion and function as a molecule involved in the regulation of inflammatory processes was reported in several studies. Investigations of PBEF/visfatin in gestational membranes suggest a function in the physiologic and pathologic pathways leading to labor. Furthermore, it was found upregulated in colorectal cancer and was brought into connection with the regulation of the cell cycle. Intra-cellular, PBEF/visfatin acts as a cytosolic enzyme involved in nicotinamide adenine dinucleotide (NAD) synthesis. This activity was shown to be important for vascular smooth muscle cell (SMC) maturation, indicating a possible involvement in vascular pathology. The important physiologic role of PBEF/visfatin is also underlined by its evolutionary highly conserved gene in different species. This review summarizes the current knowledge of the various functions of PBEF/visfatin towards involvements in pathophysiology of several diseases.