For over fifty years, the pathogenesis of May-Thurner syndrome (MTS) has been associated with chronic left common iliac vein compression resulting in the formation of intraluminal, permanent obstructive lesions. However, despite this association, the mechanism by which compression produces these lesions is unknown. Diagnostic accuracy of MTS is critical since it often afflicts young patients requiring endovascular management. This review will focus on the historical, embryological and evolutionary description of MTS and examine its development, diagnosis, clinical management and potential diagnostic errors.