New robust biocatalysts are needed to depolymerize or hydrolyze recalcitrant heterogeneous lignocellulosic biomass polymers into monomers and to convert the mixed substrates into biofuels. The ideal biocatalysts should be able to tolerate inhibitory compounds released from biomass hydrolysis and increased concentrations of the final products: ethanol or butanol. The solvent tolerance trait plays an important role in cost-effective recovery processes. Here we provide an overview of the literature of fermenting microbes in response to increased ethanol or butanol concentrations, aimed to provide insight on how microbes deal with and adapt to the ethanol and butanol stress.