Preclinical research remains an important tool for discovery and validation of novel therapeutics for gastrointestinal disorders. While in vitro assays can be used to verify receptor-ligand interactions and test for structural activity of new compounds, only whole-animal studies can demonstrate drug efficacy within the gastrointestinal system. Most major gastrointestinal disorders have been modeled in animals; however the translational relevance of each model is not equal. The purpose of this chapter is to provide a critical evaluation of common animal models that are being used to develop pharmaceuticals for gastrointestinal disorders. For brevity, the models are presented for upper gastrointestinal disorders involving the esophagus, stomach, and small intestine and lower gastrointestinal disorders that focus on the colon. Particular emphasis is used to explain the face and construct validity of each model, and the limitations of each model, including data interpretation, are highlighted. This chapter does not evaluate models that rely on surgical or other non-pharmacological interventions for treatment.