An inherited predisposition to pancreatic cancer (PC) is prevalent in about 3% of PC cases and is currently believed to occur in three distinct clinical settings, (1) hereditary tumour predisposition syndromes with an increased risk of PC such as Peutz-Jeghers syndrome and familial atypical multiple mole melanoma, (2) hereditary pancreatitis and cystic fibrosis, in which genetically determined early-age changes of the pancreas can predispose to the development of PC, and (3) familial pancreatic cancer syndrome (FPC). According to a recent consensus conference, high-risk individuals from PC-prone families should be enrolled in board-approved, prospective, controlled screening programs at expert centres. Based on the available data, prophylactic pancreatectomy is not indicated, since the underlying causative gene defect of the FPC syndrome is still unknown and the penetrance of PC in other tumour predisposition syndromes is either low or yet undetermined. In case of the diagnosis of a PC or high-grade precursor lesions, a prophylactic extension of the resection can be considered, since patients with hereditary PC often develop multifocal pancreatic lesions.