For 15 years, the debate about depleted uranium (DU) and its detrimental effects on the health of veterans of the Gulf War of 1991, on the Iraqi people and military (and subsequently on the people of Kosovo, Afghanistan, and Iraq during the second war) has remained unresolved. Meanwhile, the number of Gulf War veterans who have developed the so-called Gulf War syndrome has risen to about one-third of the 800,000 U.S. forces deployed, and unknown proportions of those involved in the subsequent wars. Uncounted civilians and personnel of other nations that fought in Iraq and other wars since 1991 have also been afflicted. The veterans have suffered from multiple serious physiological disorders and have received little or no official recognition, medical relief, or compensation. We need to take another look at this issue, using a holistic and interactive model for the toxic matrix of exposures, identifying the major roadblocks to resolving the scientific questions, and finding appropriate medical and political responses. This commentary is such an attempt.