Injection nerve injury of the lower extremity is a fairly common but incompletely quantified occurrence in medical practice. Numerous medical procedures including intramuscular injections, joint aspirations, arterial lines, and nerve blocks place these nerves at risk of injury. Some of the nerves at risk include the sciatic, femoral, saphenous, superior gluteal, posterior femoral cutaneous, and the lateral plantar, with the sciatic being the most commonly involved. The possible mechanisms of injury include direct needle trauma, pressure injury, chemical neurotoxicity, compression neuropathy, ischemia, scar formation, and allergic response. Presentation varies widely depending on the nerve injured but can be generalized to consist of paresthesia, pain, numbness, and weakness consistent with the enervated distribution of the nerve. The diagnosis of such an injury is mostly clinical but several confirmatory tests exist to quantify the damage, the most common of which are electromyography and nerve conduction study. In the case of nonsevere injuries with minimal weakness and pain, conservative therapy with pain medication, physical therapy, and regular follow-ups is recommended for 3 to 6 months. In cases with severe functional disability and/or pain or no improvement after initial conservative measures, surgical options are pursued. These include neurolysis or, in rare cases, nerve grafting. The goal of this article is to elaborate in detail the mechanisms, pathophysiology, clinical presentation, and treatment of lower extremity injection injuries in the aforementioned nerves.