Designing putative metabolic pathways is of great interest in synthetic biology. Retrobiosynthesis is a discipline that involves the design, evaluation, and optimization of de novo biosynthetic pathways for the production of high-value compounds and drugs from renewable resources and natural or engineered enzymes. The best candidate pathways are then engineered within a metabolic network of microorganisms that serve as synthetic platforms for synthetic biology. The complexity of biological chemistry and metabolism requires computational approaches to explorethe full possibilities of engineering synthetic pathways towards target compounds. Herein, we discuss recent developments in the design of computational tools for retrosynthetic biochemistry and outline the workflow and design elements for such tools.