Pancreatic cancer, pancreatic ductal adenocarcinoma, is one of the most lethal malignancies, and researchers have therefore intensified efforts directed at its early detection and management. Early detection includes an effective screening program, as pancreatic cancer is known to evolve from precursor lesions, which can be identified using currently available diagnostic modalities. A recent multicenter trial (the CAPS 3 trial) demonstrated that screening of asymptomatic individuals at high risk for pancreatic cancer frequently detects small cystic pancreatic lesions, including curable, noninvasive high-grade neoplasms. In that study, endoscopic ultrasound and magnetic resonance imaging were better at detecting pancreatic lesions than was computed tomography. On the other hand, effective screening modalities (e.g., imaging studies with measurement of biomarkers) are lacking for individuals at normal to moderate risk for this disease. Therefore, pancreatic cancer screening strategies should include identification of the population at high risk for this cancer and intensive application of screening tools with adequate sensitivity to detect early-stage disease.