Gastrointestinal stromal tumor(GIST) is the most common mesenchymal malignancy of the GI tract. The mainstay of treatment is surgery. For patients in whom complete resection is not possible, or in patients with metastatic or recurrent disease, they are unresponsive to standard chemotherapy and to radiotherapy. There has been no effective systemic treatment for unresectable GIST or metastatic disease. Gain-of-function mutations of the KIT proto-oncogene occur in up to 90% of GIST, allowing constitutive activation of tyrosine kinase (i.e. auto-phosphorylation of tyrosine residues independent of ligand-receptor binding), leading to aberrant cell division and tumour growth. Imatinib selectively inhibits the tyrosine kinase activity associated with KIT, which forms the rationale for evaluating its effects in GIST. Herein, we review recent developments in treatment for GIST and implication for optimal treatment in these patients.