In the United States, pancreatic cancer is characterized by a low 5-yr survival rate of approximately 6%, fewer than 10% of patients diagnosed with localized disease and thus candidates for “curative” surgical resection, increasing incidence and few established risk factors. Similar statistics are observed for other industrialized nations. With new evidence to suggest that pancreatic cancer develops over a number of years, markers that can better identify high risk patients and are applicable to earlier diagnosis hold promise for improving these dire statistics. Obesity is one of the few modifiable risk factors that has been associated with increased risk of pancreatic cancer and also is related to increased risk of diabetes, a condition that in turn has been associated with pancreatic cancer development. Given recent data that nearly 70% of United States adults are overweight or obese, a clarification of the complex association between obesity and pancreatic cancer may disclose targets for prevention and intervention to decrease incidence and improve prognosis of this highly fatal disease. An overview of the current epidemiology and hypothesized biological mechanisms involved in the obesity-pancreatic cancer association are presented. © 2011 Wiley Periodicals, Inc.