In this review we have presented overwhelming evidence that platelets play an important enhancing role in tumor cell-vasculature interactions and cancer metastasis. Tumor cells employ a host of mechanisms to induce platelet aggregation; vice versa, platelets make use of a spectrum of mechanisms to modulate tumor cell-EC and tumor cell-ECM interactions. Various COX and LOX metabolites are closely involved in this bidirectional modulation, thus providing us with a very promising therapeutic avenue by modifying the actions of these metabolites. On the other hand, adhesion molecules are mediators of tumor cell-platelet-EC interactions; therefore interference with these adhesion molecules and various adhesive processes either by soluble peptides, nonpeptidic analogues, or specific antibodies holds great investigational and clinical appeal.