Worldwide, over 200000 people die annually of pancreatic cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. In the United States, pancreatic cancer is the 4(th) leading cause of cancer death, and in Europe it is the 6th. Because of high fatality rates, pancreatic cancer incidence rates are almost equal to mortality rates. Pancreatic cancer is diagnosed late in the natural history of the disease, given the few early indicators of illness, and the lack of screening tests for this disease. Treatment has not improved substantially over the past few decades and has little effect on prolonging survival time. Therefore, prevention could play an important role in reducing pancreatic cancer mortality. International variations in rates and time trends suggest that environmental factors are likely to play a role in the etiology of pancreatic cancer. Variations in rates are substantial and occur even within industrialized nations. While rates have been stabilizing over the past 2 decades in many countries where they are already high, they continue to increase in countries where rates were relatively low 4 decades ago, such as Japan. In the US, the highest rates of pancreatic cancer incidence and mortality are observed among blacks, who have some of the highest rates in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. A number of studies observed a reduction in pancreatic cancer risk within a decade after smoking cessation, when compared to current smokers. With tobacco smoking as an exception, risk factors for pancreatic cancer are not well-established. Over the past 2 decades, epidemiological studies on pancreatic cancer have been plagued with methodological issues associated with studying a highly fatal disease, and inconsistent findings have hindered our understanding of the etiology of pancreatic cancer. Although familial pancreatic cancer is well-documented, the genes responsible for this condition have not been identified and are unlikely to explain more than 5-10% of all pancreatic cancer cases. Chronic pancreatitis and diabetes mellitus are medical conditions that have been consistently related to pancreatic cancer. Data from numerous studies suggest that these conditions are likely to be causally related to pancreatic cancer, rather than being consequences of the cancer. Recent cohort studies, which are less prone to biases than case-control studies, suggest that obesity increases the risk of pancreatic cancer. Other studies support the hypothesis that glucose intolerance and hyperinsulinemia are important in the development of pancreatic cancer. Other potential risk factors include physical inactivity, aspirin use, occupational exposure to certain pesticides, and dietary factors such as carbohydrate or sugar intake.