Gastrointestinal stromal tumors (GISTs) comprise <1% of all gastrointestinal tumors, but are the most common mesenchymal tumors of the GI tract. This review highlights the dramatic changes in clinical practice with regards to GIST in the last decade, with a focus on overall management and recent developments. For localized primary GISTs, surgical resection is the mainstay of therapy with the 5-year survival rate after complete resection averaging approximately 50-65%. Factors such as tumor size, mitotic rate, tumor location, kinase mutational status and occurrence of tumor rupture have been extensively studied and proposed to be predictors of outcome. Adjuvant imatinib is proposed as an option for those patients with a substantial risk of relapse. Unresectable metastatic or recurrent GIST can be treated with imatinib, with a remarkable response rate (50-70%) and prolonged survival (median progression-free survival: 18-20 months; median overall survival: 51-57 months). Sunitinib is licensed as a second-line therapy following progression on imatinib. Other promising systemic therapies include regorafenib and agents targeting the PI3K/mTOR pathway.