Gastrointestinal stromal tumor (GIST) represents the most common mesechymal tumor of the gastrointestinal tract. Discovery of the relationship between unregulated KIT kinase and GIST transformation has led to diagnostic and therapeutic targeting. Imatinib is the recommended first-line treatment of metastatic GIST. In addition, the combination of surgery and imatinib for primary GIST is indicated in the adjuvant setting of high-risk patients and there may be benefit for this combination in the neoadjuvant setting. The success of molecular targeted therapy in GIST represents an important and exciting advance in solid tumor oncology.