Overweight and/or obesity are known risk factors for many cancers and are associated with poor prognosis. Evidence for this relationship has primarily been obtained from epidemiological studies with in vitro studies characterizing potential pathways that help explain the pathological role of obesity in malignancies. Animal models provide the opportunity to more completely understand disease mechanisms and intervention strategies associated with obesity and tumorigenesis. The most widely used obese animal models result from either genetic defects or consumption of high-fat diets. Genetically obese animals used in cancer research include yellow obese mice, leptin and leptin receptor-deficient mice, and the Zucker rat. Goldthioglucose-induced obesity has occasionally been used as has been ovariectomized animals. A number of studies using rodents have explored the relationship and mechanisms of obesity and the development of mammary tumors. Additional studies have evaluated the effect of obesity in colon, skin, and prostate cancer models. These studies have provided insights into the role of body weight and tumorigenesis. However, more appropriate obesity models will be important in continuing to understand the factors associated with body weight's impact on the development of cancer and to assist in providing pharmaceutical and nutritional interventions for cancer prevention and treatment.