The most common type of sarcoma, or soft tissue tumor, gastrointestinal stromal tumors (GIST) are found throughout the intestinal tract, including the esophagus, stomach, small intestine, colon, and rectum, originating from the interstitial cells of Cajal. Historically, the mainstay of treatment for primary, resectable GIST involved surgery, but contemporary management of GIST involves a combination of surgery and targeted therapy against the membrane tyrosine kinase receptor KIT (CD117). With the development of drugs, such as imatinib, a selective anti-CD117 therapy, there has been significant improvement in GIST outcomes. The following chapter will review GIST biology, diagnosis, treatment, and surveillance.