Publisher Summary This chapter discusses the metabolism of tamoxifen by microsomal cytochrome P450 as well as flavin-containing monooxygenase. Tamoxifen (tam) is an antiestrogen and is developed as a therapeutic agent for hormone responsive (estrogen receptor-positive) breast tumors. Tamoxifen is metabolized by liver microsomes from animals and humans into a variety of compounds, such as tamoxifen N -oxide (tam- N -oxide), N -desmethyl ( N -desmethyl-tam), and 4-hydroxy (4-OH-tam) derivatives. Microsomal CYP3A catalyzes covalent binding of tamoxifen to proteins and tam- N -demethylation. This chapter describes the radiometric methods developed for detection, identification, and quantitation of several of the major tamoxifen metabolites. The chapter also describes the hepatic enzymes forming these tamoxifen metabolites. The amount of N-oxide observed in incubations of tamoxifen with liver microsomes represents the net result of the flavin-containing monooxygenase (FMO)-catalyzed N -oxide formation (forward reaction) and the N -oxide reduction (reverse reaction).