It is anticipated that unraveling the human genome will have a direct impact on the management of specific diseases. Variations or mutations in genes involved in drug metabolism or disease pathophysiology in gastroenterology and hepatology are expected to have effect on response to therapy. The spectrum of diseases is vast. Thus, we focus this review on clinical pharmacogenetics of inflammatory bowel disease, Helicobacter pylori infections, gastroesophageal reflux disease, irritable bowel syndrome, liver transplantation, and colon cancer. Although only a few genotyping tests are used regularly in clinical practice, we anticipate that in the future there will be more routine use of many of the tests described in this review.