The gastrointestinal tract provides a unique ‘window’ to access vascular structures in the mediastinum and abdomen. The advent of interventional EUS has enabled access to these structures with a standard FNA needle. FNA evolved to “FNI” with the ability to inject solutions such as sclerosants and cyanoacrylagte glue and implant devices including coils and guidewire. We can measure portal vein pressures, biopsy intravascular thrombi, collect circulating tumor cells and potentially access the heart and pericardium. EUS-guided treatment of varices has been largely reserved as ‘rescue’ therapy for refractory bleeding, but has theoretical advantages over conventional endoscopy-guided treatment. There is a growing list of novel indications for EUS-guided vascular therapy. The development of new tools designed for EUS-guided vascular therapy is needed for advancement of this fruitful and promising field.