It is likely that hereditary factors play a role in 17% or more of pancreatic cancers. Ten percent of patients have a familial history that causes disease. Another 7% have a history of apparently "sporadic" pancreatic cancer patients carry a genetic mutation that causes the disease. Kindreds, with two or more family members who have been diagnosed with pancreatic cancer and who are first-degree relatives, are considered to have familial pancreatic cancer (FPC). The inheritance pattern for FPC is usually autosomal dominant; however, the penetrance (whether a gene carrier gets the disease) is variable. The lifetime cancer risk for a gene-carrying individual from a FPC kindred can range from 5% to 100%, depending upon the gene inherited and environment-gene interactions. Smoking is the chief environmental risk factor that influences penetrance of pancreatic cancer in these kindreds. Smoking increases the risk of cancer by more than threefold and decreases the age of onset by approximately 10 years. The precursor lesion to pancreatic cancer is pancreatic intraepithelial neoplasia (PanIN), which is graded I to III depending upon the severity of the neoplastic change. Surveillance for the early detection of cancer or intraepithelial neoplasia is possible in high-risk individuals and should be performed in centers with expertise. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography can help identify those patients who have intraepithelial neoplasia and thus may warrant a tissue diagnosis. Patients who have PanIN III (carcinoma in situ) can consider the option of pancreatectomy. The widespread and multifocal nature of PanIN changes throughout the entire pancreas in high-risk patients would make a total pancreatectomy preferable over a partial surgery. Careful selection of patients, the timing of the operation, and an experienced team of gastroenterologists, pancreatic surgeons, pathologists, and diabetologists are the keys to a good surveillance program and good outcomes for the patient.