Gastrointestinal stromal tumors (GISTs) constitute the majority of mesenchymal tumors involving the gastrointestinal tract. Over the past decade, it has been recognized that these tumors have distinctive immunohistochemical and genetic features. The expression of c-Kit (CD117), a transmembrane growth factor receptor, has emerged as an important defining feature of GISTs, and the pathogenesis of these tumors may be related to c-Kit mutations. Promising preclinical results have provided the driving force for the rapid clinical development of imatinib mesylate, a selective tyrosine kinase inhibitor of c-Kit. This novel molecularly targeted therapy has produced impressive clinical responses in a large proportion of patients with advanced GISTs and is under study as an adjuvant therapy in patients with localized resectable GISTs.