In the last years, a growing interest has emerged towards understanding the role of adipocytokines in the development of cardiometabolic complications. Five years ago, visfatin/PBEF/Nampt was identified as a novel adipocytokine. In the context of metabolic disorders, extracellular visfatin/PBEF/Nampt was initially claimed as a potentially beneficial molecule due to its insulin-mimetic and glucose-lowering properties. Nevertheless, growing evidence has since then unveiled that visfatin/PBEF/Nampt may rather be a biomarker of inflammation and endothelial damage, and also a direct regulator of the cardiovascular system that modulates cell proliferation and survival, extracellular matrix, vascular reactivity and inflammation. On one side, the blockade of the deleterious cardiovascular actions of visfatin/PBEF/Nampt is being regarded as a potential approach to prevent and treat, not only cardio-metabolic complications, but also other pathologies implying excessive angiogenesis. Conversely, the administration of visfatin/PBEF/Nampt has shown beneficial effects in different ischemic conditions. Further research is required to evaluate the real value of visfatin/PBEF/Nampt as a pharmacological target.