Enzyme technology has significantly expanded in scope and impact over the past 10 years to include organic transformations in non-traditional environments. This is in part due to an increased understanding and capability of using enzyme catalysis in a wide variety of organic solvents, at interfaces, and at high temperatures and pressures. This review focuses on a relatively new but rapidly expanding research activity where in vitro enzyme catalysis is used for the synthesis of non-natural polyesters and polycarbonates. The inclination to use of enzymes for polymer synthesis has been fueled by a desire to carry out these reactions in the absence of heavy metals, at lower temperatures, and with increased selectivity. Aspects of this work that include enzyme-catalyzed step-growth condensation reactions, chain-growth ring-opening polymerizations, and corresponding transesterification of macromolecular substrates are discussed.