Metastasis is one of the most devastating aspects of cancer. It is a complex multistep processes that results in spread of tumorigenic cells to secondary sites in various organs. The actual events that are involved in metastasis are the subject of several recent reviews [1-3]. Upon growth of neoplastic cells beyond a certain mass (2 mm in diameter) an extensive vascularization through angiogenesis occurs. The new capillary network provides a supply of nutrients and gas exchange that allows further growth and development of the tumor mass. The network of the blood vessels also provides an entry site into the circulation for the neoplastic cells that detach from the tumor mass. Only a small percentage of circulating tumor cells (< 0.01%) survive travel in the circulation and arrest in the capillary beds of distant organs, extravasate and proliferate within the organ parenchyma producing a successful metastasis . Vasculature plays an important role in several steps of the metastatic process; 1) at the site of metastasis, vessels capture the cancer cell and provide the entry route into the secondary organ, and 2) through angiogenesis, vascular endothelial cells provide the supply of nutrients for the growth of the primary tumor mass and the route of intravasation. The lining of all blood vessels are covered with endothelial cells which play an active role in both processes. The metastatic properties of cancer cells have been extensively studied. Here, we will discuss the role of endothelial cells in the metastatic process with focus on their interaction with cancer cells at the site of extravasation.