Metabolic engineering is the practice of using directed genetic manipulations to rewire cellular metabolism primarily with the aim to transform the organism into a single-celled chemical factory. Using biological processes, we can produce more complex chemicals in a more sustainable way. This is particularly important for chemicals which are hard to synthesize using traditional chemistry. However, cells have evolved for growth and must be engineered to produce a single chemical at commercially viable levels. This review focuses on the strategies used to rewire cellular metabolism to produce chemicals using isoprenoid production in Escherichia coli as an example that illustrates many of the challenges faced in metabolic engineering.