The gastrointestinal track provides one of the distinct systems where multiple malignancies, including adenocarcinoma of the pancreas, esophagus and colon are each associated with obesity. The focus on possible dietary contribution as well as the role of exercise in prevention and therapy is presented in both animal model and patient based studies. Special focus is provided also on the role of genetic mutations and inflammatory pathways as drivers of these obesity related gastrointestinal malignancies.