The endothelium-derived 21 amino acid peptide endothelin-1 is one of the most potent vasoconstrictors. Endothelin-1 exerts its effects upon a variety of vascular and non-vascular cells through a direct interaction with specific receptors. Beyond its vasoconstrictive action on vascular smooth muscle cells endothelin-1 has mitogenic and pro-inflammatory properties. The present review deals with current experimental and clinical evidence for the involvement of endothelin-1 in several cardiovascular disorders with inflammatory components. We further discuss the potential clinical relevance of the endothelin system and therapeutical perspectives of anti-endothelin strategies in the treatment of cardiovascular disease.