During the past decade, there have been numerous, conflicting reports regarding the effect of perioperative blood transfusion on mortality in patients undergoing esophagectomy. In addition, the results from studies using autologous (in lieu of allogeneic) blood transfusion are not universally accepted. This article first reviews the evidence regarding the affect of blood transfusion on outcomes in other surgical fields. The underlying immunomodulatory mechanisms responsible for this effect are discussed, and the current data regarding blood transfusion and outcomes in esophageal surgery are summarized. Finally, the consequences of these results on the management of patients undergoing esophagectomy are discussed.