Imatinib (Gleevec, Glivec is a small molecule inhibitor of tyrosine kinase that has been evaluated for efficacy in patients with gastrointestinal stromal tumours (GIST). The drug is approved for the treatment of unresectable and/or metastatic, KIT-positive GIST in the US, Europe and many other countries. Imatinib has had a significant impact on the management of advanced GIST, which has traditionally had a poor prognosis, and has quickly become the first choice of treatment in the medical therapy of unresectable and/or metastatic, KIT-positive GIST. In randomised, nonblind trials, imatinib 400-800 mg/day produced complete or partial responses in up to two-thirds of patients, with long-term efficacy, and substantially prolonged progression-free and overall survival. The drug was generally well tolerated in GIST patients, including during long-term treatment. Imatinib dosages higher than 400 mg/day (up to 800 mg/day) may improve progression-free survival, with an increase in dosage benefiting some patients who show disease progression at the lower dosage, particularly in those with exon 9 mutation; however, there is also a dose-related increase in imatinib toxicity. Mutational genotype and other, non-biomolecular factors may aid in guiding imatinib therapy and predicting prognosis in GIST patients. Further data are required to evaluate the use of imatinib in adjuvant and neoadjuvant settings. Nevertheless, imatinib currently provides the most effective treatment option in the management of advanced GIST.