Following the initial description of endothelium-dependent vasoconstriction in the early 1980s, it has been exactly 25 years since efforts to identify the sequence of the endothelin gene and peptide began in May 1987, work which resulted in a landmark paper submitted to Nature in December 1987 and published on March 31, 1988. The paper opened an entirely new field of research, followed by the inception of the International Conferences of Endothelin, the first of which was organized by Sir John Vane as Chair and held as the "First William Harvey Workshop on Endothelin" in London, UK, in December of 1988. Endothelin receptor antagonism has now been firmly established for more than a decade as a new, orally active drug treatment for patients with pulmonary arterial hypertension. Since the discovery of endothelin, on average 1,000 papers per year have been published with more than 25,000 papers available today, many of them published in the conferences' Proceedings. The present issue of Life Sciences, Endothelin XII, represents a collection of papers of original research and invited lectures presented at the Twelfth International Conference on Endothelin held in Cambridge, UK, in September 2011.