Metabolic engineering is a powerful methodology aimed at intelligently designing new biological pathways, systems, and ultimately phenotypes through the use of recombinant DNA technology. Built largely on the theoretical and computational analysis of chemical systems, the field has evolved to incorporate a growing number of genome scale experimental tools. This combination of rigorous analysis and quantitative molecular biology methods has endowed metabolic engineering with an effective synergism that crosses traditional disciplinary bounds. As such, there are a growing number of applications for the effective employment of metabolic engineering, ranging from the initial industrial fermentation applications to more recent medical diagnosis applications. In this review we highlight many of the contributions metabolic engineering has provided through its history, as well as give an overview of new tools and applications that promise to have a large impact on the field's future.