This work describes the importance of tumor microenvironment in favouring tumor progression and angiogenesis. Under physiological conditions, angiogenesis is dependent on the balance of positive and negative angiogenic modulators within the vascular microenvironment and requires the functional activities of a number of molecules, including angiogenic factors, extracellular matrix proteins, adhesion molecules and proteolytic enzymes. In normal tissues, vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. Tumor angiogenesis is linked to a switch in the balance between positive and negative regulators, and mainly depends on the release by inflammatory or neoplastic cells of specific growth factors for endothelial cells, that stimulate the growth of the blood vessels of the host or the down-regulation of natural angiogenesis inhibitors. In particular, the inflammatory infiltrate may contribute to tumor angiogenesis, and there are many reports of associations between tumor inflammatory infiltrate, vascularity and prognosis. New therapeutic approaches have been developed with the aim to control tumor angiogenesis through targeting of different components of tumor microenvironment.