Sustainable biosynthesis of value-added chemicals has been gaining interest in the last two decades due to increased environmental concerns and the depletion of petroleum resources. Metabolic engineering of microorganisms has been recognized as a significant development in making such bio-based production economical at a large scale to produce chemicals, fuels, amino acids, vitamins, polymers, and many others. D-pantothenic acid (DPA) encompasses many applications in the food, cosmetic, and pharmaceutical industries. Chemical, chemo-enzymatic, and biological routes were reported for the production of DPA. High-yielding chemical and chemo-enzymatic methods of DPA synthesis are limited by using poisonous chemicals and DL-pantolactone racemic mixture formation. Alternatively, the safe microbial fermentative route of DPA production was found promising. In this chapter, we have summarized the various metabolic engineering strategies and microbial systems reported for the microbial production of DPA.