It is estimated that about 800 non-proteinogenic amino acids (NPAAs) have been identified in bacteria, fungi, plants and marine organisms, leaving the 20 proteinogenic amino acids in the minority at 4%. The existence of many hundreds of biologically active natural peptides with one or more NPAAs, reflects the ability of these particular monomers to confer some useful functional properties, not available in the basic set of 20 amino acids. The incorporation of NPAAs into peptides leads to modifications in the secondary structure that often result in improved selectivity, bioavailability, and stability. Moreover, they are extensively used in the synthesis of peptide catalysts, and functional materials. Finally, NPAAs are versatile intermediates in organic synthesis, especially in drug discovery. The broad utility of NPAAs therefore makes them one of the most important classes of organic molecules.