Hemostasis, inflammatory reactions and immunity involve close interactions between immunocompetent cells and the vascular endothelium. Cytokines, produced by and acting on endothelial cells, are mediators of the complex bidirectional interactions between leukocytes and vascular cells. Cytokines affect endothelial cell function in inflammation, thrombosis and angiogenesis, in addition to their role as accessory cells. As well as acting as targets for the action of cytokines, endothelial cells are important producers of polypeptide mediators that regulate hematopoiesis, the differentiation and proliferation of T and B cells and the extravasation of leukocytes. In this review, Alberto Mantovani and Elisabetta Dejana discuss endothelial cells as important participants in the induction and regulation of coagulation, inflammation and immunity and cytokines as crucial mediators of the symbiotic interactions between vascular cells and leukocytes.