Chronic pancreatitis is the major cause of exocrine pancreatic insufficiency which should be compensated by pancreatic enzyme replacement therapy. There are now available a great number of pancreatic enzyme preparations, but encapsulated enteric-coated microspheres and minimicrospheres are considered the enzyme treatment of choice. However, full compensation of pancreatic exocrine insufficiency with enzyme replacement therapy cannot be obtained in all patients with chronic pancreatitis.