Gastrointestinal stromal tumors (GISTs) originating in the duodenal wall constitute the most challenging localization of this gastrointestinal neoplasm. Duodenal GISTs are relatively uncommon. The prevalence of duodenal GIST is very low, accounting for 5% to 7% or less of all surgically resected GISTs. Most published reports on duodenal GIST are case reports or small case series. Consequently, the unspecific clinical manifestations, radiologic diagnosis, appropriate surgical treatment, prognostic factors, and survival constitute a subject of current controversy. This review addresses the management of duodenal GISTs trying to establish and define surgical options according to GIST localization within the duodenum. Most articles concerning duodenal GISTs state that unlike tumors involving other sites of the gastrointestinal tract, the optimal procedure for duodenal GISTs has not been well characterized in the surgical literature. However, when carefully reviewing the published literature on the subject, it was possible to identify common surgical approaches to duodenal GISTs which are fairly standard among different authors. All approaches take into account the GIST localization within the duodenal wall and its anatomic relationships to decide whether local resection or the Whipple operation should be performed. Using this knowledge, defined surgical options for duodenal GISTs according to their localization within the duodenum are being proposed. Besides the current controversy regarding the indications for the Whipple procedure, the other most important issue remaining to be addressed is the implementation of laparoscopic surgery for this challenging tumor.