The maturation of chemical synthesis during the 20 century has elevated the discipline from a largely empirical into a rational science. This ability to purposefully craft matter at the molecular level has put chemists in a privileged position to contribute to progress in neighboring natural sciences. Recently, we have witnessed another major advance in the field in which chemists use chemical and biological "synthetic" methods together to alter the structures and properties of biological macromolecules in ways heretofore unimagined. This interdisciplinary approach to synthesis has even allowed us to expand upon the defining characteristics of living organisms at the molecular level. In this perspective, we present a case study for the successful addition of new chemistries to the fundamental processes of the central dogma of molecular biology, exemplified by the expansion of the genetic code.