In spite of the great progress seen in the diagnostic and treating method for gallstone patients in this 10 years, the criteria of the operative indication for these patients have not been discussed for a long time. I wish to emphasize it is high time for us to examine a matter, since chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) have begun to be popular in Japanese medical field as an oral gallstone solubilizer. I have mentioned the different dissolving mechanism of cholesterol after the administration of CDCA or UDCA. Recently, residual gallstones are removed using the newly developed instruments, such as a duodenal fiberscope, a choledochal fiberscope, a specially designed basket catheter and a YAG laser knife. Direct gallstone solubilizer, however, is still useful for special cases where gallstones are difficult to be removed by mechanical means. In an attempt to give answer to this, we have developed and used clinically the mixed solution of d-limonene and middle chain monoglyceride for cholesterol gallstones and 90% dimethyl sulfoxide and chelating polyphosphate for bilirubin gallstones.