After decades of development, protein engineering has become sufficiently important to industry that its focus has shifted from technology innovation to application exploration. While protein engineering continues to play an important role in established industries like detergent enzymes, it also promises to provide new solutions in emerging industries such as biopharmaceuticals [evolved biologics] and renewable energy [engineered enzymes for biofuel production]. In contrast to protein engineering, synthetic biology is still in its infancy, even though the term, “synthetic biology”, was coined over thirty years ago. Synthetic biology has great potential for enabling sustainable economic growth. Indeed, synthetic pathways can produce many chemicals, including biofuels and drugs, from renewable resources. Currently, synthetic pathways are assembled from biological components culled from nature, and may not be optimal since those biological components were evolved by nature to benefit their native species’ fitness and were not customized for performance in synthetic pathways. Biological components from different species [or even different kingdoms] may not function optimally when simply put together in a pathway. Therefore, to meet industrial standards, synthetic pathways usually require optimization to produce chemicals economically, and this is where protein engineering can play significant roles. In fact, protein engineering has already been applied to optimize a number of synthetic biological components, from pathway enzymes to regulatory elements. It has also been used to balance pathway redox equivalents and control the expression of pathway genes. This editorial highlights applications of protein engineering to synthetic biology in the areas of improving enzyme activity, changing substrate or product specificity, modifying cofactor usage for redox balance, tuning protein expression, and creating scaffold multi-enzyme complexes for metabolite flux control. Due to limited space, only one to two examples are given for each application to demonstrate the concept.