Angiogenesis, the process through which new blood vessels arise from preexisting ones, plays a pivotal role during embryonal development and later, in adult life, in several physiological (e.g., corpus luteum formation) and pathological conditions, such as tumors and chronic inflammation, in which angiogenesis itself may contribute to the progression of disease. Two hallmarks of physiological angiogenesis are its brevity, and that many of the new capillary blood vessels will either regress or will go on to become ‘established’ microvessels. These mature microvessels contain quiescent endothelial cells that rest on an intact basement membrane and embedded in this basement membrane are pericytes. Thus, established microvessels have a slightly thicker wall than growing vessels. In growing microvessels, the basement membrane is disrupted and pericytes are sparse or absent. Angiogenesis is controlled by the balance between molecules that have positive and negative regulatory activity. This concept led to the notion of the “angiogenic switch,” which depends on an increased production of one or more positive regulators of angiogenesis. Angiogenic factors can exported from cells or mobilized from the extracellular matrix. The switch clearly involves more than a simple up-regulation of angiogenic activity and has thus been regarded as the result of the net balance between positive and negative regulators. Endothelial cell turnover in the healthy adult organism is low, the quiescence being maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. Various regulatory elements control the switch to the vascular phase. Angiogenesis is regulated, under both physiological and pathological conditions, by numerous “classic” factors, among which are vascular endothelial growth factor, fibroblast growth factor-2, transforming growth factors, angiopoietins, platelet-derived growth factor, thrombospondin-1, and angiostatin. In recent years, evidence has accumulated that, in addition to the classic factors, many other endogenous peptides play an important regulatory role in angiogenesis, especially under pathological conditions. Solid tumor growth occurs by means of an avascular phase followed by a vascular phase. Assuming that such growth is dependent on angiogenesis and that this depends on the release of angiogenic factors, the acquisition of an angiogenic ability can be seen as an expression of progression from neoplastic transformation to tumor growth and metastasis. Practically all solid tumors, including those of the colon, lung, breast, cervix, bladder, prostate and pancreas, progress through these two phases. The role of angiogenesis in the growth and survival of leukemias and other hematological malignancies has only become evident since 1994, thanks to a series of studies demonstrating that progression in several forms is clearly related to their degree of angiogenesis. Finally, the new possible therapeutic perspectives opened by investigations of angiogenic mechanisms will be discussed. The development of a clinical trial requires the identification and characterization of the physiological targets involved in angio-stimulatory and angio-inhibitory activities. Much research effort has been concentrated on the role of angiogenesis in cancer, and inhibition of angiogenesis is a major area of therapeutic development for the treatment of this disease. New patho-physiological concepts generated in the past few decades have given rise to the development of a large variety of new drugs to interfere with angiogenesis. The target of anti-angiogenic therapy is the vascular endothelial cell rather than the tumor cell. In fact, whereas conventional chemotherapy, radiotherapy, and immunotherapy are directed against tumor cells, anti-angiogenic therapy is aimed at the tumor vasculature and will either cause tumor regression or keep the tumor in a state of dormancy.