The existence of cholecystokinin (CCK) as a gut hormone was suggested in 1928 based on hormonal regulation of gallbladder emptying, later also on stimulation of pancreatic enzyme secretion, and modification of gastrointestinal motor activity. In 1968, a CCK peptide was purified from gut extracts and identified as a 33 amino acid peptide (CCK-33). Based on that structure, research has since expanded the insight into CCK biology remarkably: Thus, CCK was the first discovered intestinal satiety signal from gut to brain. Moreover, the CCK gene is now known to be expressed in different peptide forms not only in the gut, but much so in central and peripheral neurons, in addition to extra-intestinal endocrine cells, immune cells, cardiomyocytes, spermatogenic cells, and certain fat cells. Accordingly, CCK peptides function not only as hormones. They are also neurotransmitters, paracrine growth and satiations factors, anti-inflammatory cytokines, incretins, adipokins, myokins, potential fertility factors, and tumor markers. Thus, CCK research has now opened windows for insights into the pathophysiology of not only gallbladder disease, but also metabolic disorders, neuropsychiatric diseases, cardiac diseases, as well as the diagnosis of neuroendocrine and pediatric tumors.