Metallothionein, a low-molecular-weight protein whose apoprotein, thionein, is induced by exposure to cadmium, copper, mercury, and zinc, plays an important role in the transport and storage of heavy metals; it also provides a protective role against the toxic effects of these metals by sequestering and thus reducing the amount of the free metal ions. Interest in the detoxification role of metallothionein in fisheries research and aquatic toxicology has increased because of the increasing contamination of aquatic habitats by heavy metals. Reports of laboratory and field investigations have shown that metallothionein synthesis is induced in fishes during chronic and acute exposures to metals. There is also evidence of the presence in fish of low-molecular-weight inorganic-binding proteins that are different from metallothionein, as well as evidence that cadmium is not sequestered by metallothionein in rainbow trout Salmo gairdneri. The sequestering of metal contaminants by metallothionein and subsequent toxic effects in fish and other animals has been described by the “spillover” hypothesis, which states that once metallothionein is saturated by metals, excess metal ions spill over into other cellular compartments and cause pathological lesions. We review the literature on metallothionein in fish, and emphasize the protein's role in the detoxification and binding of metal contaminants.