Synthetic pyrethroids, a major insecticide group, are used worldwide to control agricultural and household pests. Mammalian metabolism of pyrethroids was substantially launched in the 1960s and 1970s by the research groups of Professor Casida and Sumitomo Chemical Co., which made great contributions to the elucidation of their metabolic fates. They showed that ester hydrolysis and oxidation play predominant roles in mammalian metabolism of pyrethroids and that rapid metabolism leads to low mammalian toxicity. These metabolic reactions are mediated by carboxylesterases and CYP isoforms, the resultant metabolites then undergoing various conjugation reactions. In general, there are substantially neither significant species differences in metabolic reactions of pyrethoids nor metabolic differences among their chiral isomers except with fenvalerate, one isomer of which yields a lipophilic conjugate causing toxicity.