The thoracic duct (TD) transports ingested fat, drains lymph from the gastrointestinal vascular bed, and delivers the lymph to central veins in the neck. Preliminary evidence suggests that diversion of TD lymph may mitigate the severity of end‐organ dysfunction in critical illness. Variations in the anatomy of the TD may determine whether reliable and safe cannulation of the duct, a necessary step for diversion, is possible. A systematic review was undertaken using the Google Scholar, MEDLINE, PubMed, and Scopus databases until 31st March, 2013. Both English and non‐English articles were searched for, and surgical, cadaveric, and radiologic studies were included. Fifty‐seven articles from the past 102 years were retrieved. There are significant variations in the anatomy of the TD in terms of its formation at the cisterna chyli, its course through the thorax, and its termination in the venous system. The most common site of termination is at the internal jugular vein (46%), followed by the jugulosubclavian angle (32%), and the subclavian vein (18%). An improved understanding of the anatomy of the TD would help surgeons to avoid inadvertent injury and potentially afford new opportunities for diagnosis and intervention in patients with critical illness. Clin. Anat. 637–644, 2014. © 2013 Wiley Periodicals, Inc.