Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. There are few established environmental risk factors, but a previous history of pancreatitis and exposure to tobacco and salted food appear to be the most important. A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that pancreatic adenocarcinoma can be a feature of cancer susceptibility syndromes associated with germline mutations in p16, BRCA1, BRCA2, and APC. This highlights the need for a full family history in apparently sporadic cases. Somatic mutations in p16, BRCA2, and APC have also been reported in pancreatic cancer; however, K-RAS mutations appear to be the commonest oncogenic alteration. Recent advances in our understanding of the basis of hereditary cancer syndromes may be applicable to the diagnosis, treatment, and possibly prevention of pancreatic adenocarcinoma in the future.