Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT and PDGFRα gene. Surgical resection is the only radical treatment at present, but recurrence is common. In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. For resectable GIST, operation combined with neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors can improve the prognosis of high-risk patients before or after complete resection. For unresectable GIST, targeted therapy with imatinib mesylate can effectively inhibit and ameliorate the progression of GIST.