Gastrointestinal stromal cell tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract and are frequently detected on routine endoscopy. Although only approximately 10-30% of GISTs are clinically malignant, all may have some degree of malignant potential. Preoperative determination of malignancy risk can be estimated from tumor size and location, but reliable histopathologic criteria are not currently available. Given such biological uncertainty, accurate diagnosis is essential to differentiate these lesions from other truly benign, subepithelial tumors. Endoscopic ultrasound-guided fine-needle aspiration has emerged as an important procedure to secure a tissue diagnosis of a GIST. When encountering GISTs, gastroenterologists are faced with challenging management decisions, especially in the face of small, incidentally discovered lesions. The majority of localized GISTs are managed via surgical resection, although a select few may be observed using serial endoscopic ultrasound examinations. This Review provides a general overview of GISTs, with an emphasis on their endoscopic diagnosis, the management of localized disease, and the management of incidentally discovered GISTs.