Ductal adenocarcinoma of the pancreas is characterized by extremely aggressive behavior, with an overall 5-year survival of <4%. Because conventional and specifically tailored therapeutic regimens have little impact on patient survival, epidemiological and molecular research aims at identifying and reducing risk factors. Cigarette smoking, obesity, diabetes mellitus, and chronic pancreatitis are amenable to medical prevention or therapy. Heavy alcohol consumption is an inconsistent single risk factor for pancreatic cancer but may promote carcinogenesis by increasing the risk of diabetes mellitus or chronic pancreatitis. For various agents, the key carcinogenic effect is probably an inflammatory response in the pancreatic tissue. On the molecular level, mutations of oncogenes and tumor suppressor genes, as well as various epigenetic alterations, such as overexpression of growth factors and their receptors, are important in tumorigenesis. Complete and safe surgical resection, together with adjuvant therapy, offers prolonged survival, with 5-year survival rates of approximately 25%. However, for unresectable or disseminated disease, which constitutes the vast majority of cases, treatment is palliative. Despite increasing knowledge about the molecular pathology of pancreatic cancer and despite advances in treatment, the overall course of the disease is dismal, and reinforced efforts to reduce incidence and improve outcome are needed desperately.