Naturally occurring iodine (₅₃I) consists of one stable isotope, ¹²⁷I, and is a mononuclidic element for atomic weight. Radioisotopes of iodine are known from ¹⁰⁸I to ¹⁴⁷I.

The longest-lived of those, ¹²⁹I, has a half-life of 16.14 million years, which is too short for it to exist as a primordial nuclide. It is, however, found in nature as a trace isotope and universally distributed, produced naturally by cosmogenic sources in the atmosphere and by natural fission of the actinides. Today, however, most is artificial as fission product; like krypton-85 the contribution of past nuclear testing and of operating reactors are dwarfed by release from nuclear reprocessing.

All other iodine radioisotopes have half-lives less than 60 days, and four of these are used as tracers and therapeutic agents in medicine – ¹²³I, ¹²⁴I, ¹²⁵I, and ¹³¹I. All industrial use of radioactive iodine isotopes involves these four. In addition, one other isotope has a half-life in the same range – ¹²⁶I (12.93 days; decays almost equally to tellurium or to xenon).

The isotope ¹³⁵I has a half-life less than seven hours, which is inconveniently short for those purposes. However, the unavoidable in situ production of this isotope is important in nuclear reactor control, as it decays to ¹³⁵Xe, the most powerful known neutron absorber, and the nuclide responsible for the so-called iodine pit phenomenon.

In addition to commercial production, ¹³¹I (half-life 8 days) is one of the common radioactive fission products of nuclear fission, and thus occurs in large amounts inside nuclear reactors. Due to its volatility, short half-life, and high abundance in fission products, ¹³¹I (along with the short-lived iodine isotope ¹³²I, which is produced from the decay of ¹³²Te with a half-life of 3 days) is responsible for the most dangerous part of the short-term radioactive contamination after environmental release of the radioactive waste from a nuclear power plant. For that reason, iodine supplements (usually potassium iodide) are given to the populace after nuclear accidents or explosions (and in some cases prior to any such incident as a civil defense mechanism) to reduce the uptake of radioactive iodine compounds by the thyroid.

Radioisotopes of iodine are called radioactive iodine or radioiodine. Dozens exist, but about a half dozen are the most notable in applied sciences such as the life sciences and nuclear power, as detailed below. Mentions of radioiodine in health care contexts refer more often to iodine-131 than to other isotopes.

Of the many isotopes of iodine, only two are typically used in a medical setting: iodine-123 and iodine-131. Since ¹³¹I has both a beta and gamma decay mode, it can be used for radiotherapy or for imaging. ¹²³I, which has no beta activity, is more suited for routine nuclear medicine imaging of the thyroid and other medical processes and less damaging internally to the patient. There are some situations in which iodine-124 and iodine-125 are also used in medicine.

Due to preferential uptake of iodine by the thyroid, radioiodine is extensively used in imaging of and, in the case of ¹³¹I, destroying dysfunctional thyroid tissues. Other types of tissue selectively take up certain iodine-131-containing tissue-targeting and killing radiopharmaceutical agents (such as MIBG). Iodine-125 is the only other iodine radioisotope used in radiation therapy, but only as an implanted capsule in brachytherapy, where the isotope never has a chance to be released for chemical interaction with the body's tissues.