Gastrointestinal stromal tumors (GISTs) are rare neoplasms. The advent of electron microscopy and immunohistochemistry has led to the realization that these tumors originate from a pleuropotential cell known as the interstitial cell of Cajal (ICC). The morphologic features demonstrated as most predictive of recurrence or metastases are tumor size and mitotic rate. There is oncologic justification for minimally invasive resection techniques with gross margins for GISTs. Minimally invasive resection provides advantages to patients in terms of morbidity and recovery. A variety of endoscopic, laparoscopic, and hybrid techniques are described for surgically excising GISTs in different anatomic locations.