This paper overviewed risk factors of pancreatic cancer. Both genetic and environmental factors may be playing significant roles in the development of pancreatic cancer. Cigarette smoking has been established as a major risk factor for pancreatic cancer, based on findings from almost all epidemiological studies. Long-term smoking cessation may reduce the risk. The evidence that alcohol drinking and coffee consumption increase the risk is not sufficient, although an association with higher level of consumption remains a possibility. Diabetes mellitus, long-standing diabetes in particular, may be a risk factor for pancreatic cancer. Individuals with hereditary pancreatitis or non-hereditary chronic pancreatitis are possibly at increased risk of pancreatic cancer. Higher intake of meat and fat may be associated with an increased risk, while consumption of fruits/vegetables appears to have a protective effect. Individuals with mutations or deletion in such genes as K-ras, p16, p53, DPC4, and BRCA2 increased the risk of developing pancreatic cancer. Cigarette smoking may play a role in the development of these mutations.