V ascular disease is the leading cause of mortality and morbidity in the United States. Coronary artery disease, cerebrovascular disorders, pulmonary venous thromboembolism, and systemic and pulmonary hypertension account for one third of the national annual mortality. Traditionally, the practice of cardiology has emphasized the diagnosis and treatment of the sequelae of these disorders. This approach has been exemplified by major advances in cardiovascular surgery, interventional catheter techniques, and heartlung transplantations, to name a few. Recently, major conceptual shifts have occurred in our approach to vascular disease. Increasingly, we recognize the importance of preventive cardiology and the need to under-stand the fundamental mechanisms mediating these disorders. Specifically, there is an explosion of new information on the complex and intricate processes that maintain homeostasis of the vessel wall and the pathobiological events that result in vascular diseases. We believe that the future in the management of vascular disease will depend on thedevelopment of novel diagnostic and therapeutic strategies based on our growing knowledge of vascular biology. This article is intended to review the latest developments in vascular biology and provide our perspectives on the future of the emerging discipline of vascular medicine. The concept of vascular biology and medicine has evolved dramatically from William Harvey's1 original description of the circulation in which the vasculature was conceived as a passive conduit transporting blood to and from vital organs. It is now recognized that the vasculature is a complex organ capable of sensing its environment, transducing signals to the cells within the vasculature orto the surrounding tissue, and synthesizing local mediators that promote functional or struc-tural responses. A constant feature of these interactions is the delicate balance between countervailing mechanisms. Vascular cells produce vasoconstrictors as well as vasodilators, procoagulants as well as anticoagulants,