Metabolic pathologies such as Type 2 Diabetes have become a major health problem for worldwide populations. Unfortunately, efforts to cure and especially to prevent these significant global problems have so far been met with disappointment. Recently, the involvement of the gut-derived hormonal dysregulation in the development of obesity-related disturbances has been intensively studied. For instance, studies of gut-derived peptides such as peptide YY 3-36, glucagon-like peptide-1, oxyntomodulin and, more recently, ghrelin have significantly improved our understanding of mechanisms underlying weight and metabolic regulation. Even though early reports of the existence of secretin, the first peptide hormone to be described, date back as far as 1825, so much and yet so little is still known about its physiological role in mammals, including humans. However, recent years have provided a better understanding of how the release of secretin is regulated by enteral secretagogues. On the other hand, most basic questions about its role in the post-prandial regulation of metabolic functions in normal and pathophysiological conditions remain to be elucidated. The present work intends to review the physiology of secretin along with its central and peripheral outcomes on metabolic functions.