Secretin was discovered by Starling & Bayliss in 1902. Three years later the hormone concept and hormonal regulation were described and early regulatory physiology took a major step forward. After several years of unsuccessful investigations, secretin was isolated with new chromatographic techniques and subsequently synthesised in the 1960s. Radioimmunoassays in the 1970s confirmed the final endocrine role of secretin. Cloning and molecular hybridisation in the 1990s have identified the size of production, precursor, genetic structure, and evolutionary relation to other gastrointestinal peptides. In addition, the secretin receptor has been described. In recent years, synthetic secretin has been applied in the functional and structural diagnostics of pancreatic function and in experimental therapy. Although it was the first bioactive substance to be identified as a hormone, our knowledge of secretin today, 100 years on, is still incomplete.