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Xylitol has been recognized by the US Department of Energy (DOE) as one of the top 12 value-added chemicals obtained from biomass, with a world market of 200,000 tonnes per year. The global xylitol market is expected to reach a value of US$ 1 Billion by 2026 growing at a compound annual growth rate (CAGR) of 5.8% during 2021–2026. Historically, the commercial xylitol production process has been dependent on the chemical hydrogenation of xylose. Several xylitol production plants, mainly in China that use the chemical process have had to reduce their production capacity to address regulations governing sustainability and environmental standards. In this chapter, key challenges and possible solutions for fermentative xylitol production at commercial scale are discussed in terms of: (1) Feedstock supply for commercial production plants; (2) Industrial biomass pretreatment; and (3) Lessons learned from …