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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract and are thought to arise from precursors of the interstitial cells of Cajal. GISTs can arise anywhere in the GI tract, but most commonly originate from the stomach and small intestine. The majority of GISTs occur as a result of activating mutations in two receptor protein tyrosine kinases: KIT and/or platelet-derived growth factor receptor-α. Mutational analyses allow for predicting patient prognosis and treatment response. Clinical presentations can vary from no symptoms, typical in the case of small incidentally found tumors, to GI bleeding, abdominal discomfort, and ulcer-related symptoms when the tumor is enlarged. Imaging plays a critical role in the diagnosis and management of these tumors with multiphasic computed tomography serving as the imaging modality of choice. Magnetic resonance imaging and positron emission tomography-computed tomography can serve as imaging adjuncts in lesion characterization, especially with liver metastases, and subsequent staging and assessment for treatment response or recurrence. Surgical resection is the preferred management for small GISTs, while tyrosine kinase inhibitors − imatinib mesylate and sunitinib malate − serve as crucial molecular-targeted therapies for locally advanced and metastatic GISTs. This review article highlights the clinical presentation, pathology and molecular cytogenetics, imaging features, and current management of GISTs.