Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that are found throughout the gastrointestinal tract. They are molecularly characterized by gain-of-function mutations in oncogenes, including c-KIT and PDGFRα. They are believed to arise from the interstitial cells of Cajal within the myenteric plexus of the gut. Many studies have characterized the incidence of GIST in the United States, Europe, and Asia. The annual incidence reported in the literature varies by region: 3.2–6.8 cases per million persons in the United States; 2.1–14.5 cases per million persons in Europe; and 11.3–19.7 cases per million persons in Asia. However, many of these earlier studies were confounded by additional histologies confused with GIST, including leiomyoma, leiomyosarcoma, or neurofibroma. Across multiple studies, it has been shown that GIST is more common in older patients, males, Blacks, and Asian/Pacific Islanders. The average age at diagnosis ranges from 62 to 75, with peak incidence in the 8th decade of life. In regard to tumor-related characteristics, the stomach is consistently the most common tumor location followed by the small intestine. Finally, risk factors associated with death include increased age at diagnosis, male sex, Black race, and the presence of regional and/or metastatic disease. Taken together, our understanding of the patient- and disease-related characteristics of GIST has evolved over the last two decades. As further insights are gained into the biology of this disease, we continue to translate these into a better understanding of the epidemiology of GIST.