Amino acids are among the most important molecules in nature since they play central roles both as building blocks of proteins and as intermediates in metabolism. The amino acid sequence dictates protein folding, the native three dimensional structure, and protein stability. Furthermore, the peculiar chemical properties of the amino acids residues forming the active site and their interplay determine the peculiar environment that allows for protein function and regulation. All amino acids found in proteins, except glycine, possess a stereogenic center at the alpha-carbon atom. Millions of years of evolution have resulted in the virtually complete homochirality of such a stereogenic center, i.e. the L-enantiomer, in mammals. This selection of the L-amino acids by nature is generally considered to be a result of chance. Since the cornerstone of the protein-ligand recognition is the multi-point attachment theory, it turns out that the configuration of the alpha-carbon atom of amino acids strongly affects the protein-ligand interaction. Many enzymes that convert L- to D- amino acids are validated targets. In this review, the structure and function of these enzymes are presented as well as the existing compounds that affect their activity