One critical step in tumor metastasis is tumor cell adhesion to the endothelium forming the microvessel wall. Understanding this step may lead to new therapeutic concepts for tumor metastasis. Vascular endothelium forming the microvessel wall and the glycocalyx layer at its surface are the principal barriers to, and regulators of the material exchange between circulating blood and body tissues. The cleft between adjacent ECs (interendothelial cleft) is the principal pathway for water and solutes transport through the microvessel wall in health. It is also suggested to be the pathway for high molecular weight plasma proteins, leukocytes and tumor cells across microvessel walls in disease. Thus the first part of the review introduced the mathematical models for water and solutes transport through the interendothelial cleft. These models, combined with the experimental results from in vivo animal studies and electron microscopic observations, are used to evaluate the role of the endothelial surface glycocalyx, the junction strand geometry in the interendothelial cleft, and the surrounding extracellular matrix and tissue cells, as the determinants of microvascular transport. The second part of the review demonstrated how the microvascular permeability, hydrodynamic factors, microvascular geometry and cell adhesion molecules affect tumor cell adhesion in the microcirculation.