The hydrogen element exists naturally in the form of three isotopes, sharing the same number of proton and electron, which is equal to 1, but not that of neutrons, which ranges from 0 to 2. In order, these isotopes are protium, commonly said light hydrogen and indicated with 1 1H or simply H; deuterium, commonly heavy hydrogen indicated with 2 1H or D; and tritium, 3 1H or T. Naturally, deuterium abundance is 0.0115%, whereas tritium is rare and radioactively unstable. Protium, deuterium and tritium form diatomic molecules bonding together, which can be homonuclear, H2, D2 and T2, or heteronuclear, HD, HT and DT. Homonuclear molecules can exist in either an ortho modification, oH2, oD2, oT2, or a para modification, pH2, pD2, pT2. Hydrogen has the largest isotope effects principally due to the largest differences in the relative mass of its isotopes. Isotope effects are differences in chemical and physical properties arising from differences in the nuclear mass. In particular, lighter hydrogen molecules are characterized by higher vapour pressures than heavier ones; in other words, lighter molecules are more volatile. Among the isotope separation techniques, distillation is adopted in industrial applications because of the advantages of achieving high separation degrees and of processing large quantities of fluids. Distillation is based on the different vapour pressures of the components to be separate and; hence, it requires the coexistence of liquid and vapour phases. Coexistence occurs in the cryogenic range of 10-40 K for molecular hydrogen. The number of cryogenic distillation plants constructed for deuterium and tritium separation is small due to their limited market. One example is the deuterium plant built in Germany in the late 1960s, and another the tritium plant in Canada in the late 1980s. Both plants proved the possibility to achieve high purities, exceeding 99.8%, as well as high separation factors. Today, deuterium is employed mostly as constituent of heavy water as neutron moderator for a number of nuclear fission reactors; it is also utilized for the preparation of nuclear weapons or as a non-radioactive tracer in chemical and metabolic reactions. Tritium is used instead as a radioactive tracer in chemistry and biology. Both deuterium and tritium are adopted for the research on the physics of matter and, notably, they have been selected for the future International Thermonuclear Experimental Reactor nuclear fusion reactor.