Sulfoconjugation (Sulfation or Sulfonation) is an important reaction in the phase II biotransformation of a wide number of endogenous and foreign chemicals, including: drugs, toxic chemicals, hormones, and neurotransmitters. The reaction is catalyzed by the members of the cytosolic sulfotransferase (SULT) superfamily, consisting of ten functional genes in humans. Sulfation reaction in living cells is reversed by sulfatase, which hydrolyses the sulfonated conjugates. It has a major role in regulating the endocrine status of an individual by modulating the activity of steroid hormones, their biosynthesis, and the metabolism of catecholamines. Sulfonation is a key reaction in the body's 'chemical' defense against xenobiotics. Although the primary function of sulfoconjugation is to permit detoxification of the compound, it also results in the activation of chemical procarcinogens, such as certain dietary and environmental agents into carcinogens. In this review, we summarize our current understanding of the structure of mammalian cytosolic sulfotransferases and their role in human steroid associated cancers and in the bioactivation of chemical carcinogens.