Quadrilateral space syndrome (QSS) arises from compression or mechanical injury to the axillary nerve or the posterior circumflex humeral artery (PCHA) as they pass through the quadrilateral space (QS). Quadrilateral space syndrome is an uncommon cause of paresthesia and an underdiagnosed cause of digital ischemia in overhead athletes. Quadrilateral space syndrome can present with neurogenic symptoms (pain and weakness) secondary to axillary nerve compression. In addition, repeated abduction and external rotation of the arm is felt to lead to injury of the PCHA within the QSS. This often results in PCHA thrombosis and aneurysm formation, with distal emboli. Because of relative infrequency, QSS is rarely diagnosed on evaluation of athletes with such symptoms. We report on 9 patients who presented at Mayo Clinic with QSS. Differential diagnosis, a new classification system, and the management of QSS are discussed, with a comprehensive literature review. The following search terms were used on PubMed: axillary nerve, posterior circumflex humeral artery, quadrilateral space, and quadrangular space. Articles were selected if they described patients with symptoms from axillary nerve entrapment or PCHA thrombosis, or if related screening or imaging methods were assessed. References available within the obtained articles were also pursued. There was no date or language restriction for article inclusion; 5 studies in languages besides English were reported in German, French, Spanish, Turkish, and Chinese.