Nerve injury following peripheral nerve blocks (PNB) is a rare but significant complication that requires careful evaluation and management. This article explores the differential diagnosis, pathophysiology, risk factors, and preventive strategies for PNB-related nerve injury (PNI). The incidence of postoperative neurological symptoms (PONS) is up to 15%, though permanent deficits are rare. Factors increasing the risk of PNI include pre-existing neuropathy, metabolic disorders (e.g., diabetes), mechanical compression, and ischemia. The double crush theory highlights how underlying nerve compromise can predispose patients to additional injury. Prevention strategies include ultrasound guidance, injection pressure monitoring (<15 psi), peripheral nerve stimulation, and careful needle selection. The classification of nerve injuries (Seddon and Sunderland) helps predict prognosis, ranging from neuropraxia with full recovery to neurotmesis with permanent damage. Electrophysiological studies are typically delayed by 2–3 weeks to detect Wallerian degeneration. Patient counseling and follow-up are crucial, with most injuries resolving over time. The role of vasoconstrictors, intraneural injections, and adjuncts in nerve damage is also discussed. A multidisciplinary approach involving neurology, imaging, and pain management is recommended for persistent deficits, ensuring optimal patient outcomes.