omega-Hydroxy fatty acids (-HFAs) are of great interest because they provide the long carbon chain monomers in the synthesis of polymer materials due to the location of the hydroxyl group close to the end of the first methyl carbon. -HFAs are widely used as building blocks and intermediates in the chemical, pharmaceutical, and food industries. Recent achievements in metabolic engineering and synthetic biology enabled Escherichia coli to produce these fatty acids with high yield and productivity. These include (i) design and engineering of the -HFA biosynthetic pathways, (ii) enzyme engineering to enhance stability and activity, and (iii) increase of tolerance of E. coli to toxic effects of fatty acids. Strategies for improving product yield and productivity of -HFAs and their related chemicals (e.g., ,-dicarboxylic acids and -amino carboxylic acids) are systematically demonstrated in this review.