Quadrilateral space syndrome is an infrequent, recently established neurovascular compression syndrome affecting young active adults. With this syndrome, the neurovascular bundle, consisting of the posterior humeral circumflex artery (PHCA) and the axillary nerve, is compressed by fibrotic bands as it traverses the quadrilateral space. Symptoms result from compression of the axillary nerve, not from PHCA occlusion. Because of the vague, often nonspecific, clinical presentation of patients with quadrilateral space syndrome, diagnosis is challenging and requires a high index of suspicion from the orthopedist. Subclavian arteriography confirms the diagnosis. Treatment is usually conservative; operative management is reserved for selected patients. A posterior approach with detachment of the deltoid and teres minor muscles is recommended for surgical decompression and for lysis of fibrous tissue. We report two cases of persistent quadrilateral space syndrome in young adults, treated surgically, with 2-year follow-up. In the present report, diagnostic criteria, pathology, management, operative technique, and recent literature are also reviewed.