Digestive system malignancies are quite common, accounting for 25% of deaths from cancer in the European Union. Various etiological factors of carcinogenesis include hereditary mutations and susceptibility polymorphisms, inflammation due to infectious agents, environmental and dietary factors. Transgenic, knockout or mutant animal models are very useful in reproducing cancers of the digestive tract that occur in humans. They offer the opportunity to study the disease phenotype and the function of the underlying mechanisms of carcinogenesis. In addition, animal models are valuable tools in cancer treatment attempts with the combined use of gene targeting or chemotherapy. This review illustrates the importance of the numerous animal models that have been developed by various methods in order to study carcinogenesis in the digestive tract and test potential therapeutic treatments.