Purpose of Review: Postoperative nerve injury after nerve block is complex and multifactorial. The mechanisms, etiologies, and risk factors are explored. This review article conducts a literature search and summarizes current evidence and best practices in prevention of nerve injury. Recent Findings: Emerging technology such as ultrasound, injection pressure monitors, and nerve stimulators for peripheral nerve block have been incorporated into regular practice to reduce the rate of nerve injury. Studies show avoidance of intrafascicular injection, limiting concentrations/volumes of local anesthetic, and appropriate patient selection are the most significant controllable factors in limiting the negative consequences of nerve block. Summary: Peripheral nerve injury is an uncommon occurrence after nerve block and is obscured by surgical manipulation, positioning, and underlying neural integrity. Underlying neural integrity is not always evident despite an adequate history and physical exam. Surgical stress, independently of nerve block, may exacerbate these neurologic disease processes and make diagnosing a postoperative nerve injury more challenging. Prevention of nerve injury by surgical teams, care with positioning, and avoidance of intrafascicular injection with nerve block are the most evidence-based practices.