Gastrointestinal stromal tumors are the most common mesenchymal neoplasm of the gastrointestinal tract and diagnostic rates have been increasing with greater utility of advanced imaging technology. It is believed that most of these tumors originate from the interstitial cells of Cajal due to gain-of-function mutations in c-KIT and/or PDGFRA that encode for respective receptor tyrosine kinases. Because the tumors can arise anywhere along the gastrointestinal tract, symptoms can vary. Endoscopy is most frequently used in diagnosis, especially with the utility of endoscopic ultrasound that can allow for fine needle aspiration of the tumor. Histologically, gastrointestinal stromal tumors can display a range of morphological features and are often characterized as spindled, epithelioid, or mixed types. Diagnosis can be further elucidated with the use of immunohistochemical or molecular analyses. Pathologic staging of gastrointestinal stromal tumor is based on tumor size, lymph node involvement, and metastatic involvement, and a risk stratification system for progressive disease is available that considers anatomic site of origin, mitotic rate, and tumor size. While surgical resection has an important role in localized tumors with the goal of complete resection, imatinib in the adjuvant or neoadjuvant setting has revolutionized therapy by being a tyrosine kinase inhibitor that can directly target many tumors. Treatment will vary by patient, and multidisciplinary teams can aid in deciding the optimal medical and/or surgical therapies in each case.