Intraosseous infusions are a valuable means of establishing intravascular access in pediatric emergencies. We report a case of compartment syndrome from prolonged intraosseous infusion (53 hours). We postulate that chemical irritation from medications, infections, the tenuous nature of intraosseous infusions, and the use of infusion pumps may all play a role in the development of compartment syndrome. We recommend that, when possible, intraosseous lines be used only temporarily until more permanent vascular access is established, that lines that do not flow with gravity be removed, and that drugs known to cause chemical burns be used with caution. In addition, the use of x-ray and hourly measurement of leg circumference may help to determine whether a line is still in place. Also, given the changing circumstances and technology under which intraosseous infusions are used, new prospective studies of their complications are needed.