Imatinib is a tyrosine kinase inhibitor directed against the KIT and the PDGF-alpha receptors. Imatinib has proven efficacy in the treatment of metastatic GIST with a response rate achieving 70%, but treatment with imatinib alone is not curative. The median progression-free survival is about 2 years. In locally advanced GIST, primary treatment with imatinib proved to be safe and feasible in several cohort studies. The goal of any curatively intended surgical treatment for GIST is R0 resection. Therefore, neoadjuvant treatment with imatinib can be recommended if tumor-free margin resection is doubtful. After R0 resection of GISTs with intermediate or high risk of relapse, preliminary data indicate that imatinib administered for at least 1 year reduces the risk of relapse and may improve the prognosis. However, no mature survival data from randomized studies have been published thus far. Therefore adjuvant treatment with imatinib is not yet approved nor is it a standard of care at this stage. The inclusion of patients with intermediate- and high-risk resected GIST into clinical studies is strongly recommended.