This issue is devoted to the role of angiogenesis in cardiovascular disease. The lead article and the three respondent articles give excellent reviews on various aspects of modern angiogenesis research. Although this field of research initially emerged from investigations into tumor metastases, it has its roots in cardiovascular embryology. Already in 1893, Thoma1 described the principles of vascular development in an elegant monograph. He defined three rules for vascular development: (i) the number of vessels that grow in a tissue is determined by genetic constitution and the metabolic needs of the tissue; (ii) the diameter of a vessel depends on the flow of blood through its lumen; and (iii) the thickness of the vessel wall is determined by transmural tension. These basic rules remain unchallenged even in this early part of the 21st century. The past two decades have witnessed a tremendous increase in knowledge of the molecular mechanisms underlying these basic features of vascular growth...