Despite the huge number of drugs on the market and recent advances in pharmacotherapy, only a few substances are available for the prevention of gastrointestinal tumors--most of which are not approved for this indication or not validated in appropriately designed randomized trials. General recommendations include lifestyle modifications such as avoidance of smoking, only moderate consumption of alcohol, regular physical exercise and a nutrition rich in fresh fruits and vegetables with limited meat. A global eradication therapy for Helicobacter pylori would be desirable to prevent gastric carcinoma, but this does not seem feasible from the socio-economic point of view. Therefore, at least patients at high risk should be screened and this pathogen eradicated, preferentially in their youth. Hepatitis B vaccination of newborns to prevent the development of hepatocellular carcinoma has already been established in Germany; a specific antiviral therapy should be offered to all patients with hepatitis B or C infections, taking into consideration the risks associated with this treatment. The use of non-steroidal anti-inflammatory drugs (NSAIDs) to prevent gastrointestinal malignancies cannot generally be recommended and should be restricted to patients at high risk and to clinical studies. However, the appropriate substance, dose and duration of NSAID therapy are still being debated.