FMO (EC 1.14.13.8) is an ancient and conservative group of enzymes present in all living organisms without exception. FMO is a microsomal flavoprotein that oxidizes molecules containing nucleophilic heteroatoms of nitrogen, sulfur, phosphorus, or selenium. FMO do not oxidize physiologically essential nucleophiles. The prosthetic group of FMO is FAD. In addition, the enzyme uses NADPH and molecular oxygen, most often catalyzing the formation of monooxygenated substrates, NADP+, and water as by-products of the reaction. In humans, the FMO1–4 genes are closely located on the chromosome, which in mammals was the result of an earlier gene duplication, and are localized on the chromosome 1q24.3, while FMO5 is located on the chromosome 1q21.1. FMO5 is the first enzyme that appeared in mammals, since FMO5 genes feature a higher nucleotide composition variation among different vertebrate species. In humans, hFMO1–5 show various tissuespecific expression patterns. Along with cytochromes P450 (CYP), FMOs are the most important component of phase I biotransformation of xenobiotics. FMO and CYP show similarities in tissue-specific distribution, molecular weight, and substrate specificity. Unlike CYP, FMOs do not require the presence of a substrate to start the catalytic cycle. An important difference between FMO and CYP is that the former is not subject to either rapid induction or inhibition. Despite the overlapping substrate specificity, the catalysis of FMO and CYP produces different metabolites with different toxicological and pharmacological properties. Unlike CYP, FMOs are not usually induced or inhibited by xenobiotics, which suggests that drugs that are primarily metabolized by FMOs will be less sensitive to drug interactions.