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Environmental concerns arising from the release of greenhouse gases have stimulated the search for more sustainable technologies, including bioethanol production from lignocellulosic biomass. However, the rigid and complex structure of this biomass means that lignocellulosic biomass conversion to bioethanol requires numerous stages, such as pretreatment, enzymatic hydrolysis, and fermentation, not to mention the underlying costs and time, especially during enzymatic hydrolysis and fermentation. For all these reasons, this technology still is not attractive for industrial use. Response Surface Methodology (RSM) has helped to optimize the bioethanol production stages with a view to obtaining an economical process and to improving process efficiency. This review presents an overview of RSM and analyzes how this tool can be applied to study and to optimize the factors that influence lignocellulosic biomass …