Anti-angiogenic agents potentially have broad applications in the clinic. Although most agents now in development are intended ultimately for use as anti-cancer drugs, patients with a range of disorders may benefit in the longer term. The signal recognition and transduction processes involved in controlling angiogenesis are complex and are likely to be dependent on the status of the target endothelial cell in a specific organ or tissue. In this review, the authors focus on signaling interactions that affect microvascular endothelium and the role of growth factors and their receptor tyrosine kinases in the regulation of microvessel physiology as they relate to the angiogenic process.