Endothelial cells are an important source of eicosanoid formation in the cardiovascular systems. All major pathways of eicosanoid production have been demonstrated in endothelial cells, yielding significant amounts of prostacyclin (PGI2), PGE2, PGF2 alpha, thromboxane A2, leukotrienes and a number of hydroxy fatty acids. The regulation of eicosanoid formation by endothelial cells is poorly understood. There is evidence that precursors, such as arachidonic acid or prostaglandin endoperoxides, may also be provided by other cell types. Endothelial cell-derived eicosanoids are involved in the regulation of local vessel tone, intravascular platelet activation, cell locomotion and, eventually, cell proliferation. Most of the available information considers PGI2. This compound is the quantitatively dominating eicosanoid in endothelial cells. Major actions of PGI2 include inhibition of platelet activation and aggregation, relaxation of arterial vessels and inhibition of growth-factor release. There is probably a tight interaction with other biologically active mediators which needs further evaluation. This also applies to the clinical significance of eicosanoid-related pathways for the mechanism of action of cardiovascular drugs, such as organic nitrates or acetylsalicylic acid. The unique property of the eicosanoid system to become activated only in response to stimulation, the local nature of this reaction, the multiplicity of products formed and the short half-time of most of them are currently the most significant obstacles to define the role of endothelial cell-derived eicosanoids in clinical practice.