The development of an effective therapy for patients with gastrointestinal stromal tumors (GISTs) is one of the most interesting and exciting stories in modern oncology. A single molecularly targeted drug, imatinib mesylate, has been the standard therapy for 15 years, changing a completely chemoresistant disease with a life expectancy measured in months (for those with advanced disease) to an illness with a mean overall survival of greater than 5 years. A significant fraction of patients who receive imatinib (approximately 25%) live with their cancer for what many experts conclude will likely be their normal, expected life spans.