The therapy of choice of resectable GIST is complete surgical removal of the tumor. Lymphadenectomy is not necessary. Following R0 resection of the primary tumor long term follow up of the patients is essential. In case of high risk primary (large tumor, high proliferation rate) patients are encouraged to participate in clinical trials administering imatinib mesylate as adjuvant therapy. Patients with non-resectable, residual, locally recurrent or metastatic GIST should be treated with 400 mg/day imatinib mesylate (Glivec). In case of primary imatinib resistance patients are advised to participate in clinical trials of new tyrosine kinase inhibitors. In secondary imatinib resistance the daily dose of the drug should be increased up to 800 mg. If further progression occurs one of the new tyrosine kinase inhibitors can be tested in clinical trials. If an originally non-resectable GIST can be rendered resectable with "neoadjuvant" imatinib therapy, removal of the tumor should be considered. If resection is not possible imatinib treatment should be continued until progression or toxicity. Efficacy of imatinib therapy can be monitored by CT, MR or PET scans. Treatment of patients with GIST is multidisciplinary, needing strong cooperation among surgical- and medical oncologists, pathologists and imaging specialists. The complex therapy of GIST patients is ideally performed at specialized oncological centers.