In recent years, zebrafish has emerged as a useful animal model for biomedical research. The deciphering of the zebrafish genome has revealed that many of the enzymes involved in the metabolism of endogenous compounds and xenobiotics are conserved between zebrafish and humans. This review summarizes the information currently available concerning the zebrafish cytosolic sulfotransferases (SULTs), a group of phase II enzymes that have been proposed to be involved in the regulation and homeostasis of key endogenous compounds and the detoxification of xenobiotics. To date, 20 zebrafish SULTs that fall into six major SULT gene families have been identified. Of the 20 SULTs 18 have been cloned, expressed, purified and characterized. These zebrafish SULTs were shown to exhibit differential substrate specificities for endogenous compounds such as monoamine transmitters, steroid/thyroid hormones and bile salts, as well as xenobiotics including environmental toxicants and drugs. These findings provide a foundation for using zebrafish as a model for investigating further the physiological, pharmacological, and toxicological involvement of the SULTs.