This chapter discusses the diagnosis, evaluation and management of esophageal perforation and mediastinitis. About a third of patients present with atypical symptoms or signs including sepsis, peritonitis, respiratory distress, fever, pneumo/hydrothorax, fulminant shock, and multi-system organ failure. Approximately 17% of esophageal perforations are diagnosed only at autopsy. 90% of patients have findings suggestive of perforation on simple chest radiography. A contrast study such as esophagography with Gastrograffin should be performed if perforation is suspected. Although barium has superior sensitivity, it causes a worsened mediastinal/peritoneal inflammatory response if a leak is present. In addition, Gastrograffin is recommended because it does not obscure visualization during endoscopy. Computed tomography (CT) of the chest and abdomen with oral contrast may better define the leak, assess complications, and exclude other diagnoses.