Since its discovery in 1988, there has been an enormous amount of interest in endothelin-1 (ET-1) and its regulatory and growth-promoting role in cardiovascular physiology. Evidence from the Sixth International Conference on Endothelin, held in Montreal in October 1999, continued to demonstrate that the endothelin system is an important therapeutic target in cardiovascular disease, with promising results in animal studies now being confirmed by clinical trials in humans. In addition, many new and exciting roles for ET-1 were presented, suggesting that ET-1 antagonism may have a broader therapeutic potential than previously imagined.