The SULT1C enzymes are a relatively under-studied branch of the cytosolic sulfotransferase (SULT) multigene family. Concrete information about SULT1C tissue-specific expression, substrate preference, role in physiology and regulation is just emerging in the literature. The role of SULT1Cs in normal physiology is uncertain, but SULT1C-catalyzed sulfonation of thyroid hormones may be a mechanism to titrate the pre-receptor levels of biologically active thyroid hormone in target tissues. Both rat and human cytosolic SULT1Cs are most noted for their ability to bioactivate potent procarcinogens such as N-hydroxy-2-acetylaminofluorene. This implicates a possible role for the SULT1Cs as modulators of environmental carcinogen exposure and determinants of neoplastic transformation. In humans, the SULT1Cs are likely to function physiologically in cell proliferation and organogenesis pathways during development, as SULT1Cs appear to be preferentially expressed during fetal life. In recent years, the SULT1C nomenclature as presented in the literature has undergone major changes in response to updated genomic information. The purpose of this review is to summarize the current literature on the SULT1Cs and to clarify perspectives on SULT1C species differences, tissue-specific expression, nomenclature and role in pathophysiology. The ultimate goal is to understand the undiscovered impact of SULT1C expression on hormone homeostasis and xenobiotic toxicity during human development and as a prelude to disease development later in life.