Regional anesthesia has been considered a great tool for maximizing post-operative pain control while minimizing opioid consumption. Post-operative rebound pain, characterized by hyperalgesia after the peripheral nerve block, can however diminish or negate the overall benefit of this modality due to a counter-productive increase in opioid consumption once the block wears off. We reviewed published literature describing pathophysiology and occurrence of rebound pain after peripheral nerve blocks in patients undergoing orthopedic procedures. A search of relevant keywords was performed using PubMed, EMBASE, and Web of Science. Twenty-eight articles (n = 28) were included in our review. Perioperative considerations for peripheral nerve blocks and other alternatives used for postoperative pain management in patients undergoing orthopedic surgeries were discussed. Multimodal strategies including preemptive analgesia before the block wears off, intra-articular or intravenous anti-inflammatory medications, and use of adjuvants in nerve block solutions may reduce the burden of rebound pain. Additionally, patient education regarding the possibility of rebound pain is paramount to ensure appropriate use of prescribed pre-emptive analgesics and establish appropriate expectations of minimized opioid requirements. Understanding the impact of rebound pain and strategies to prevent it is integral to effective utilization of regional anesthesia to reduce negative consequences associated with long-term opioid consumption.