Although gunshot wounds are relatively common, lead toxicity associated with extra-articular retained missiles (EARMs) is an uncommon, yet potentially devastating, complication. Although the risk of lead toxicity with intra-articular retained missiles is well known, EARMs are routinely left in situ or only removed in selected circumstances secondary to the relatively rare occurrence of complications. We first describe a patient with systemic lead poisoning associated with retained lead fragments after a gunshot-induced left femoral shaft fracture. We then performed a systematic review of the literature to answer the following questions: (1) In the setting of retained extra-articular bullets and/or bullet fragments, is regular monitoring and/or surveillance of lead levels in the blood routinely indicated? and, if so, (2) what are the selected factors that portend an increased risk for elevations in blood lead levels in the setting of retained extra-articular bullets and/or bullet fragments? The systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, of the English language literature utilizing Medline (PubMed), EMBASE, Cochrane, and CINAHL on the topic of lead poisoning, retained bullet, and gunshot wound, and then searched for additional references by manually searching of bibliographies of the included references. Studies were included if they provided clinical data on one or both of our study questions; included studies were evaluated using the accepted levels of evidence. Routine monitoring or surveillance of lead levels in blood is recommended in all cases of EARM at the time of hospital admission and again at discharge, followed by monthly intervals until 3 mo post-injury and then again at 1 yr post-injury. The studies identified demonstrated significant risk factors for elevated blood lead levels in the setting of EARM, which included the number of retained missiles and concomitant fracture. Recommendations for routine monitoring and surveillance of blood lead levels in all cases of EARM are conflicting, but such monitoring appears to be warranted given that the potential risks and morbidity associated with systemic lead poisoning are outweighed by any potential harm of short-term, blood lead level monitoring. Outside of concomitant fracture, the evidence for making further clinical recommendations regarding selected risk factors that portend an increased risk for elevated blood lead levels after gunshot injury is weak. Larger level II and III studies are needed to determine the indications for and frequency of lead toxicity screening after retained EARM.