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Energy sources for powering automobiles, homes, and industries directly or indirectly originate from petroleum, a finite and nonrenewable resource. Because petroleum reserves cannot be replenished, an important question arises: how can this critical energy source be replaced once it becomes depleted to ensure long-term energy security? For this reason, various nations have launched programs aimed at developing renewable alternative energy sources. These renewable sources include solar, wind, hydropower, and biofuels. Among them, only biofuels provide a liquid energy form that is compatible with the engines of automobiles, airplanes, and home generators. Currently, biofuels such as ethanol are produced from corn and sugarcane, which also serve as human food. To reduce competition between these food crops and their use as substrates for biofuel production, alternative nonfood feedstocks, such as lignocellulosic biomass, are being promoted to produce fuels and chemicals. However, depolymerization of lignocellulosic biomass (LB) to generate fermentable sugars requires pretreatment and hydrolysis, processes that often produce cellulosic inhibitors and elicitors. This chapter, therefore, provides an overview of lignocellulose-derived microbial inhibitory compounds (LDMICs) released during pretreatment and hydrolysis of LB and discusses their effects on the growth of fermenting microorganisms and the production of fuels and chemicals. The chapter also highlights some non-LB derived microbial inhibitors and elicitors, including the concentrations at which some of these compounds transition from fermentation elicitors to inhibitors.