In this article we consider the factors responsible for the unique nature of the pericellular matrix of solid tumors and we discuss the role of alterations of tumor blood vessel structure. We examine the role of VEGF (vascular endothelial growth factor), a factor controlling permeability of capillaries, plasma protein extravasation, and the formation of a fibrin barrier. We discuss how this barrier could be destroyed by metalloproteinases bound on the surface of endothelial cells migrating through the matrix and how these enzymes are responsible for the activation of gelatinases that destroy basement membranes. The process called tubulogenesis, which gives rise to hyperpermeable tumor capillaries, will also be described. Alterations of the blood vessel structure leading to hypoxia of the matrix, and accumulation of plasma proteins and of blood cells will be treated. Finally, we review some of the strategies that might exploit this knowledge about the nature of the tumoral matrix for designing novel anticancer treatments.