Gastrointestinal stroma tumors (GIST), an abdominal stroma entity, are characterized by a gain-in-function mutation in the c-kit proto-oncogen (CD117). Initial treatment should aim at complete removal of the primary tumor (R0 resection), which almost never develops lymphatic metastases. Distant metastatic spread mainly involves the peritoneal cavity and the liver. In patients with metastatic disease, treatment with the tyrosine kinase inhibitor imatinib mesylate is indicated and very effective. Systemic chemotherapy and external beam radiation must be considered ineffective. Patients requiring multivisceral resection for primary tumor removal quickly develop tumor recurrence and could benefit from preoperative treatment with imatinib. To assess the response to treatment, 18F-FDG positron emission tomography or gadolinium-enhanced magnetic resonance imaging have proven helpful, as the conventional criteria of tumor shrinkage according to WHO standards are rarely met. Primary tumors are classified into four risk categories according to size and mitotic activity. The possible advantages of adjuvant treatment are currently under investigation through international randomized trials. Patients who develop extensive remission of metastatic disease should be evaluated individually for resection of the tumor remnants. Even the resection of single progressive lesions (newly developed mutations) should be considered in carefully selected patients if the remaining tumor can be controlled by continued imatinib treatment.