Identification of high-risk individuals, genetic counseling, and informed consent are important components of a screening program for familial pancreatic cancer. Screening high-risk individuals with imaging tests, such endoscopic ultrasound (EUS) and computed tomography (CT), can lead to the detection and treatment of predominantly asymptomatic early pancreatic neoplasms, as well as extra-pancreatic tumors. These pancreatic neoplasms consist of resectable, mostly branch-type non-invasive intraductal papillary mucinous neoplasms (IPMNs). EUS can visualize these very early IPMNs as focal duct ectasias or cysts. EUS features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to multifocal pancreatic intraepithelial neoplasia (PanIN). No one molecular marker is ready for "prime time" screening of high-risk individuals. Translational studies are underway to discover novel biomarkers for IPMNs, PanIN-3 lesions, or microinvasive adenocarcinoma, which are likely to be cured by timely intervention. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic neoplasia and timely intervention results in decreased pancreatic cancer incidence and mortality in high-risk individuals.