Biliary pain is commonly reported in household surveys with the presumed cause being gallstones. When gallstones are absent or other abnormalities as a potential cause of similar pain do not exist, a different approach is necessary. Although trans-abdominal ultrasound can detect stones down to 3-5 mm, the advent of endoscopic ultrasound provides an even better definition for microlithiasis of < 3 mm. Duodenal aspiration of bile can further detect cholesterol microlithiasis or bilirubin granules, another potential source of biliary-type pain and perhaps even pancreatitis. Only in this way can acalculous gallbladder disease be clearly defined. The percentage of cholecystokinin-stimulated gallbladder emptying has been reputed to be the most sensitive diagnostic test for 'biliary dyskinesia', but abnormality of gallbladder emptying can be due to a smooth muscle defect of the gallbladder itself or heightened tone in the sphincter of Oddi. The value of surgical intervention has not been clearly established. The advent of laparoscopic cholecystectomy, however, has increased the number of patients with acalculous biliary disease who undergo surgery. Surgery is best done using impaired gallbladder emptying as the criterion for operation with improved outcome. Often, following cholecystectomy, biliary pain does not resolve the so-called 'post cholecystectomy syndrome'. Absence of the gallbladder as a pressure reservoir leaves the sphincter of Oddi as the prime determinant of bile duct pressure. Sphincter of Oddi dysfunction also exists in patients with an intact biliary tract and may become evident following cholecystectomy. Biliary manometry has clarified who might benefit from sphincterotomy. Choledochoscintigraphy is a non-invasive preliminary test. Advent of visceral hypersensitivity and better definition of this entity has shown, that in some of these patients with type III sphincter of Oddi, dysfunction appears to reside in duodenal hyperalgesia. It is clear that improved criteria are required to perform gallbladder emptying and better techniques to detect visceral hypersensitivity. Nonetheless, functional biliary pain in the absence of gallstone disease is a definite entity and a challenge for clinicians.