Esophagojejunal anastomosis leakage is one of the major complications after total gastrectomy for gastric cancer and is an independent predictor of survival. Our aim is to systematically review the literature and discuss the reported therapeutic approaches to identify the best therapeutic approach. Pubmed, EMbase, Cochrane Library, CILEA Archive, BMJ Clinical Evidence, and Up ToDate databases were screened limiting the research to articles written in English from January 1992 through December 2013. This way a total of 474 manuscripts were retrieved for furthermore evaluation. Eleven manuscripts were considered eligible and the study is focused on those works. We analyzed a total of 3,893 patients and 114 cases of esophagojejunal anastomosis leakage. Different treatments were grouped into three main categories: conservative approach (66 cases), endoscopic approach (21 cases), and surgical approach (27 cases). The overall mortality rate is 26.32 per cent and surgical approach showed the higher rate. According to the reported data, a complete resolution of the leakage can be achieved in an interval ranging from 7 to 28 days in the group treated conservatively. Conservative approach should always be considered as the treatment of choice. Reoperation may be necessary in case of wide dehiscence or when other treatments fail; therefore, the high mortality rate related to this procedure is due to the comorbidities of patients undergoing relaparotomy. Finally, endoscopic approach with endoclips seems promising but needs furthermore studies.