Management of patients with gastrointestinal stromal tumor (GIST) typically involves a combination of surgical, pathologic, and pharmacologic interventions. Gastroenterologists are often the first specialists to encounter patients presenting with GIST and are therefore responsible for facilitating early intervention strategies. Although patients with gastric or small-bowel GISTs typically present with symptoms, a diagnosis of GIST should be considered whenever a submucosal lesion is seen endoscopically. Visualization by standard endoscopy often can determine tumor location and size, although endoscopic ultrasound (EUS) is the most accurate imaging technique for submucosal lesions. Biopsy techniques that yield sufficient tumor samples for diagnostic studies, such as EUS-guided fine needle aspiration, are essential, although other approaches such as EUS-guided core needle biopsy may increase diagnostic yield for subepithelial lesions. Pathology assessment should include immunohistochemical staining for KIT and possibly DOG1 expression, and mutational analysis can have prognostic and predictive value for certain patients. R0 resection is the goal for patients with localized or potentially resectable tumors, which often can be accomplished by laparoscopic resection, even for larger tumors. Medical oncologists play a key role in assessing risk of recurrence after resection and optimizing tyrosine kinase inhibitor therapy in the adjuvant or metastatic setting. Cytoreductive surgery may have value for patients with recurrent or metastatic GIST who exhibit stable disease or respond to tyrosine kinase inhibitor therapy. A coordinated multidisciplinary approach over the course of the disease will serve to enhance communication among GIST team members, reduce risk of progression, and optimize outcomes.