Posterior epidural intervertebral disc migration and sequestration (PEIMS) is a rare and debilitating complication of degenerative disc disease. Radiological differential diagnosis is often challenging, complicating the accurate planning of appropriate treatment strategies. We systematically reviewed the literature on PEIMS, focusing on clinical-radiological features and available treatments. PubMed, Scopus, Web of Science, and Cochrane were searched to include studies reporting clinical data of patients with PEIMS. Clinical characteristics, treatment strategies, and functional outcomes were analyzed. We included 82 studies comprising 157 patients. Median age was 54 years (range, 19-91). PEIMSs occurred spontaneously (49.7%) or acutely in patients with underlying progressive degenerative disc disease (50.3%). The most common symptoms were lower-back pain (77.1%) and radiculopathy (66.2%), mainly involving the L5 nerve root (43.8%). PEIMSs were mostly detected at MRI (93%) and/or CT (7%), frequently located in the lumbar spine (81.5%). Median maximum PEIMS diameter was 2.4 cm (range, 1.2-5.0). Surgical debulking was completed in 150 patients (95.5%), sometimes coupled with decompressive laminectomy (65%) or hemilaminectomy (19.1%). Median follow-up time was 3 months (range, 0.5-36.0). Post-treatment symptomatic improvement was reported in 153 patients (97.5%), with total recovery in 118 (75.2%). All 7 patients (4.5%) who received conservative non-surgical management had total clinical recovery at ≤ 3 months follow-ups. PEIMS is a challenging entity that may severely quality-of-life in patients with degenerative disc disease. Surgical removal represents the gold standard to improve patient’s functional status. Spine fusion and conservative strategies proved to be effective in some cases.