The United Nations has consistently supported the elimination of nuclear weapons, frequently referring to the effects of the 1945 bombings of Hiroshima and Nagasaki, Japan. Despite awareness of the severe effects of the use of nuclear weapons on targeted or adjacent populations, at a practical level the UN system has not specifically planned how it would respond to assist the victims of nuclear weapons. Moreover, the current humanitarian system is largely unprepared for the special challenges of such an event. This is significant for three reasons: First, the probability of the explosion of a nuclear weapon in populated areas may be low, but such an event is not impossible; there are many ways nuclear weapons might be detonated, either deliberately or inadvertently, with severe humanitarian consequences. Second, in assisting the victims, the UN-coordinated humanitarian system could put its own personnel at risk. Third, although any humanitarian response would at least in part be only palliative, and prevention remains the only adequate response, organizations within the Red Cross and Red Crescent Movement have already begun considering these issues and the UN needs to be ready to work with them. There are many ways in which the humanitarian system could better prepare for the challenges that even a single nuclear explosion would pose, and such preparation is consistent with the UN’s mission and the secretary-general’s recent call for all feasible steps to be taken to avoid systemic humanitarian failures.