Enrichment
Natural uranium typically contains about 0.7 percent U-235, the isotope of uranium that is most likely to fission (split) and therefore the easiest to use to produce energy. (Almost all the rest is U-238, which fissions very rarely or only when high-speed neutrons interact with it, but most nuclear reactors in operation today purposefully slow down neutrons to make use of the more easily fissionable U-235.) This means that uranium usually must be enriched before it can be used as nuclear fuel. However, reactors employing very efficient neutron moderators, such as heavy water or pure graphite, can use natural uranium as fuel. In contrast, light water reactors employing light, or normal, water as a moderator, require enriched uranium fuel.

Reactors fueled by natural uranium and moderated by graphite or heavy water can be used to produce weapons-grade plutonium. Spent fuel from these reactors can be reprocessed to extract this plutonium for use in nuclear weapons.

The enrichment process takes advantage of the fact that UF₆ molecules containing U-235 are slightly lighter than molecules of hex containing U-238. If UF₆ gas is forced through a porous barrier or spun rapidly through a centrifuge, some of the lighter molecules with U-235 can be separated from the heavier molecules with U-238. If this process is repeated many times, the final product will be UF₆ with a high enough percentage of  U-235 to be used as nuclear fuel. Most nuclear reactors require fuel containing about 3.5 percent U-235. Uranium enriched to lower than 20 percent U-235 is known as low-enriched uranium (LEU). This enrichment level, set by the International Atomic Energy Agency in consultation with member states, is a benchmark above which the material is of particular proliferation concern.

Uranium enriched to 20 percent U-235 or higher is considered highly enriched uranium (HEU), which can be used in nuclear weapons. The higher the percentage of enrichment, the easier it is to use the uranium to make a nuclear bomb because less material would be required to form a critical mass for a nuclear explosion. The uranium used in nuclear weapons is typically enriched to 90 percent U-235 or higher. If HEU is not properly accounted for and protected, there is a danger that it could be stolen, smuggled, or sold for use in nuclear weapons. Most authorities conclude that Pakistan produced its nuclear arsenal by enriching uranium. South Africa had built six nuclear weapons using about 80 percent enriched HEU, but dismantled them.

Some types of reactors used for scientific research, and most reactors that power nuclear submarines, use fuel made from HEU. If this fuel is not adequately protected, it could be stolen by or sold to terrorists and used to make improvised nuclear explosives.