Despite the wealth of knowledge available on uranium (U) metabolism, excretion, and toxicity in animals and humans exposed to natural and enriched U in 1991 [1–3], there was minimal information available on depleted uranium (DU) toxicity when U.S. Gulf War soldiers were exposed to DU for the first time under battlefield conditions. In multiple friendly-fire incidents involving munitions containing DU penetrators and DU armored tanks, U.S. soldiers were exposed by inhalation, ingestion, and wound contamination to aerosolized DU oxides formed when DU penetrators struck U.S. Bradley and Abrams tanks. In addition, some soldiers in or on the U.S. tanks were hit by fine metal fragments that still remain embedded in their muscle tissue. Precise predictions of the short- and long-term health effects of DU under these unique exposure conditions were not fully possible despite the substantial toxicological database 106available, due to the limited information available on the size and solubility of the DU oxides formed under these battlefield conditions. In addition, knowledge gaps existed regarding the local and systemic effects of the DU embedded fragments.