Over the past century, Escherichia coli has become one of the best studied organisms on earth. Features such as genetic tractability, favorable growth conditions, well characterized biochemistry and physiology, and availability of versatile genetic manipulation tools make E. coli an ideal platform host for development of industrially viable productions. In this review, we discuss the physiological attributes of E. coli that are most relevant for metabolic engineering, as well as emerging techniques that enable efficient phenotype construction. Further, we summarize the large number of native and non-native products that have been synthesized by E. coli, and address some of the future challenges in broadening substrate range and fighting phage infection. •The well characterized physiology of E. coli allows for rapid strain development.•A plethora of genetic techniques have been developed for genomic edits in E. coli including the λ-Red recombinase system, CRISPR, and MAGE.•A wide variety of chemicals have been produced by E. coli both in the laboratory and for industrial scale production.