The perivascular adipose tissue (PVAT) has been recently recognized as an important factor in vascular biology, with implications in the pathogenesis of cardiovascular diseases. The cell types and the precursor cells of PVAT appear to be different according to their location, with the component cell type including white, brown, and beige adipocytes. PVAT releases a panel of adipokines and cytokines that maintain vascular homeostasis, but it also has the ability of intervention in the pathogenesis of the atherosclerotic plaques development and in the vascular tone modulation. In this review, we summarize the current knowledge and discuss the role of PVAT as a major contributing factor in the pathogenesis of ischemic coronary disease, hypertension, obesity, and diabetes mellitus. The new perspective of PVAT as an endocrine organ, along with the recent knowledge of the mechanisms involved in dysfunctional PVAT intervention in local vascular homeostasis perturbations, nowadays represent a new area of research in cardiovascular pathology, aiming to discover new therapeutic methods.