The gastrointestinal tract provides a unique “window” to access vascular structures in the mediastinum and abdomen. The advent of interventional endoscopic ultrasound (EUS) has enabled access to these structures with a standard fine-needle aspiration (FNA) needle. Sclerosants, cyanoacrylate, and coils can be delivered through the lumen of the FNA needle. EUS-guided treatment of gastric varices has theoretical advantages over conventional endoscopy-guided treatment. Controlled studies are needed to determine the role of EUS-guided treatment for primary and secondary prevention of variceal bleeding. There is a growing list of novel indications for EUS-guided vascular therapy that include portal vein angiography and pressure measurements, intrahepatic portosystemic shunt placement, and micro coil embolization of vascular structures. Additionally, access and therapy of the heart and surrounding structures appears feasible.