The three-phase bone scan has been shown to be useful in the diagnosis of osteomyelitis, with a high sensitivity and specificity under optimal conditions. However, there are many causes of focally-increased uptake of Tc-99m diphosphonates in the extremities that may mimic infection, especially when there is increase on all three phases. Radiolabeled leukocyte scintigraphy is often performed in this clinical setting, although many pitfalls resulting in false-positive scans still remain. The authors present three cases of gouty arthritis in which skeletal scintigraphy illustrates this lack of specificity. Further causes of increased extremity uptake are reviewed, with attention to those that have been reported to show an increase on all three phases of the bone scan. Additional factors that can improve the specificity of the bone scan are discussed, as are the panoply of more recent scintigraphic approaches aimed at distinguishing infection from aseptic inflammation in the extremity. Unfortunately, no nuclear medicine procedure to date has proven itself to be reliably specific for infection.