Accurate staging of pancreatico-biliary cancer is essential for surgical planning and for identification of locally advanced and metastatic disease that is incurable by surgery. The complex regional anatomy of the pancreatico-biliary system makes histologic diagnosis of malignancy at this region difficult. The ability to position the endoscopic ultrasound transducer at endoscopy in direct proximity to the pancreas and the bile duct, combined with the use of fine-needle aspiration, enables accurate preoperative staging of cancer, especially cancer too small to be characterized by CT or MRI. Endoscopic ultrasonography (EUS) identifies patients unlikely to be cured by surgery due to vascular invasion or regional nodal metastasis, thereby limiting procedure-related morbidity and mortality. This article focuses on the utility and recent advances of EUS in the evaluation of pancreatico-biliary cancer.