Recent evidence indicates that obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers, including those of the colon, prostate, and pancreas. Obesity, physical inactivity, visceral adiposity, hyperglycemia, and hyperinsulinemia are relatively consistent risk factors for colon cancer and adenoma. Also, patients with type 2 diabetes mellitus have a higher risk of colon cancer. For prostate cancer, the relationship to obesity appears more complex. Obesity seems to contribute to a greater risk of aggressive or fatal prostate cancer but perhaps to a lower risk of nonaggressive prostate cancer. Furthermore, men with type 2 diabetes mellitus are at lower risk of developing prostate cancer. Long-standing type 2 diabetes increases the risk of pancreatic cancer by approximately 50%. Furthermore, over the past 6 years, a large number of cohort studies have reported positive associations between obesity and pancreatic cancer. Together with data from prediagnostic blood specimens showing positive associations between glucose levels and pancreatic cancer up to 25 years later, sufficient evidence now supports a strong role for diabetes and obesity in pancreatic cancer etiology. The mechanisms for these associations, however, remain speculative and deserve further study. Hyperinsulinemia may be important, but the role of oxidative stress initiated by hyperglycemia also deserves further attention.