Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. GIST occur predominantly in the stomach and less frequently in the extraduodenal small bowel, the colon, and the rectum; rarely, GIST can be found in the esophagus and the duodenum. Due to their biological behavior, the primary treatment goal for localized primary GIST is complete resection, without the need for lymphadenectomy or wide resection margins. Thus, gastric wedge resections and segmental resections of the small bowel are the most common surgical procedures for treating primary GIST. Surgical therapy of extensive primary tumors or of metastatic or recurrent GIST should be integrated into a multimodal therapeutic concept that includes targeted therapy with tyrosine kinase inhibitors, such as imatinib.