As knowledge of the human genome grows, there will be a direct impact on the management of specific diseases. Within gastroenterology and hepatology, there has been a change in the understanding of how variations or mutations in genes involved in drug metabolism or disease pathophysiology affect response to therapy. This review discusses the application of clinical pharmacogenetics to the following diseases and disorders: inflammatory bowel disease, Helicobacter pylori infections, gastroesophageal reflux disease, irritable bowel syndrome, functional dyspepsia, liver transplantation and colon cancer. Although only a few genotyping tests are regularly used in clinical practice, it is anticipated that studies will propel the routine use of many of the tests described in this review, in the future.