Transferases and chiral discrimination Transferases are enzymes that transfer a group from a donor compound to another acceptor compound. The groups commonly transferred by various transferases are alkyl or aryl groups, single carbon groups, aldehyde or ketonic groups, acyl groups, nitrogenous groups, phosphorus-containing groups, sulfur-containing groups, and selenium-containing groups. As per the recommended names, these enzymes could be termed either acceptor-group transferase or donor-group transferase. If the chemical structure of the group being transferred is chiral, a number of transferases ef†ciently exclude the possibility of the incorporation of a particular chiral form (in many cases, the corresponding nonnatural form) of the group (when chirality is present in the respective group). For example, the active site of the peptidyl transferase at ribosome speci†cally incorporates the L-amino acid and it is practically impossible to misincorporate D-enantiomer. Such selectivity is important for the †delity of the biochemical reaction so that the product with natural chirality is generated rather than the incorporation of the wrong enantiomer. This is essential for the production of the fully functional protein structure. Although the availability of the D-enantiomer is negligible in today’s predominantly homochiral world with the exclusive presence of L-amino acid in many organisms, it is still important to arrive at an understanding of the origin of the †delity mechanism. The active site structure of the organisms is the structure that developed chiral selectivity through evolution. Understanding of the †delity mechanism is expected to help design strategies for targeted protein synthesis. In this chapter, we discuss the features of chiral discrimination exhibited by peptidyl transferase, telomerase, HIV-1 reverse transcriptase, and nuclear DNA polymerase.