The past decade has witnessed substantial progress in our understanding of the molecular mechanisms of tumor cell interactions with vascular endothelium and extracellular matrix, important events in the metastatic process. This progress has been made possible by the identification and functional characterization of a large number of adhesion molecules involved in tumor cell-vasculature interactions. Essentially, most of the adhesion receptor families so far reported, including integrins, cadherins, selectins, immunoglobulins, and proteoglycans, have been implicated in various stages of tumor progression and metastasis. Disseminating cancer cells often employ ectopic expression of certain adhesion molecules to facilitate their interaction with the vessel wall and matrix, typical examples being the expression of integrins alpha IIb beta 3 and alpha L beta 2 and immunoglobulin family members PECAM-1, ICAM-1, and N-CAM in solid tumor cells. The expression of adhesion molecules in cancer cells and vascular endothelial cells is spatiotemporally regulated, in a dynamic fashion, by a wide diversity of bioactive molecules such as eicosanoid 12(S)-HETE. Recent data indicate that most adhesion molecules, integrins in particular, participate in various signaling functions such as the induction of calcium fluctuation and protein tyrosine phosphorylation. The importance of adhesion molecules in tumor metastasis is also evidenced by their involvement in other important parameters of metastasis such as angiogenesis. Collectively, the accumulated literature suggests that interference with adhesion and signaling represent a future direction for the development of anticancer and antimetastasis therapeutic protocols.