With a high demand for increasingly diverse chemicals, as well as sustainable synthesis for many existing chemicals, the chemical industry is increasingly looking to biosynthesis. The majority of biosynthesis examples of useful chemicals are either native metabolites made by an organism or the heterologous expression of known metabolic pathways into a more amenable host. For chemicals that no known biosynthetic route exists, engineers are increasingly relying on automated computational algorithms, as described here, to identify potential metabolic pathways. In this chapter, we review a broad range of approaches to predict novel metabolic pathways. Broadly, these can rely on biochemical databases to assemble known reactions into a new pathway or rely on generalized biochemical rules to predict unobserved enzymatic reactions that are likely feasible. Many programs are freely available and immediately useable by non-computationally experienced scientists.