Endoscopic ultrasound (EUS) has become well established as a diagnostic modality in gastrointestinal cancer staging. It offers high-resolution imaging and fine-needle biopsy, which is essential in tumor and nodal staging of gastrointestinal cancers. In the recent decade, however, many therapeutic applications of EUS have become possible. Currently, interventional EUS endoscopy involves celiac plexus neurolysis, pseudocyst drainage, and intratumoral fine-needle injection therapy for inoperable pancreatic malignancy. Emerging techniques include the accurate endoscopic delivery of radioactive beads to localize tumor therapy as well as other therapies, such as radiofrequency ablation or cryotherapy. Diagnostic and therapeutic access to the biliary tree and pancreatic duct is increasingly being used successfully in failed endoscopic retrograde cholangiopancreatography (ERCP) procedures. This review discusses these procedures and several evolving future applications, including vascular access and EUS-guided enteral anastomosis.