Pancreatic cancer has a dismal prognosis, and early detection through screening is likely to be our best hope to improve survival. The relatively low incidence of pancreatic cancer and the insensitive screening techniques available currently render this approach prohibitively expensive and inefficient in the general population. Screening has begun, however, in the subset of patients at the highest risk of disease, such as those with inherited risk due to familial multiorgan cancer syndromes or in familial groupings of pancreatic cancer with yet unidentified genetic abnormalities, termed familial pancreatic cancer. Screening is currently done at several large centers in the world, each with a unique multidisciplinary approach and series of screening tests. Endoscopic ultrasound has emerged as the most promising imaging test given its high sensitivity and potential for tissue sampling. However, this potential to detect and cure early lesions should be carefully balanced with the risk of overtreatment, especially in view of the morbidity and mortality of pancreatic surgery. Additional experience to help determine the best screening strategy is greatly needed. Screening should therefore be done at experienced centers with multidisciplinary teams of specialists and in the context of research protocols.