Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors, with specific histological characteristics. These tumors are resistant to conventional radiation and chemotherapy treatment and therefore, patients with unresectable or metastatic GIST have a poor prognosis. Imatinib, a c-kit tyrosine kinase inhibitor, has recently been found to be highly effective for patients with advanced GIST. We report on 13 consecutive patients, aged 43-78 years, treated at our center between the years 2001-2004. Two patients were given imatinib as neoadjuvant treatment and the other 11 patients were treated with palliative intent. Response to imatinib was evaluable in 11 out of 13 patients. Objective response was seen in 10 patients (91%) and included complete response in two of them (18%). After a follow-up of 4-33 months (median 7 months), the median time to tumor progression has not yet been reached. The treatment was generally well tolerated. The most common adverse events included edema of the periorbital and lower extremities. We conclude that imatinib is a safe and highly effective therapy for GIST patients with unresectable or metastatic disease, providing new hope for durable remission in these patients.