A calutron is a mass spectrometer originally designed and used for separating the isotopes of uranium. It was developed by Ernest Lawrence during the Manhattan Project and was based on his earlier invention, the cyclotron. Its name was derived from California University Cyclotron, in tribute to Lawrence's institution, the University of California, where it was invented. Calutrons were used in the industrial-scale Y-12 uranium enrichment plant at the Clinton Engineer Works in Oak Ridge, Tennessee. The enriched uranium produced was used in the Little Boy atomic bomb that was detonated over Hiroshima on 6 August 1945.

Isotope separation is the process of concentrating specific isotopes of a chemical element by removing other isotopes. The use of the nuclides produced is varied. The largest variety is used in research. By tonnage, separating natural uranium into enriched uranium and depleted uranium is the largest application. In the following text, mainly uranium enrichment is considered. This process is crucial in the manufacture of uranium fuel for nuclear power plants, and is also required for the creation of uranium-based nuclear weapons. Plutonium-based weapons use plutonium produced in a nuclear reactor, which must be operated in such a way as to produce plutonium already of suitable isotopic mix or grade.