Contemporary relevance of biofuelsas an attractive replacement for liquid fossil fuels has rekindled global interest in the conversion of cellulosic biomass — the most abundant renewable source of carbon and energy on our planet.  In order to achieve efficient systems for such a formidable substrate, we take guidance from the native enzyme systems of the microbes that have evolved to rid the natural environment of plant-derived wastes. These cellulolytic bacteria and fungi employ a diversity of contrasting but complementary mechanisms for the hydrolysis of cellulose and other related complex plant cell wall polysaccharides. This presentation covers various known microbial paradigms for attacking the recalcitrance problem in the conversion of cellulosic biomass to soluble sugar by-products en route to a biofuels-based society. These include free enzyme systems, cellulosomes, multifunctional enzymes, and cell-anchored enzyme systems. It is anticipated that the biosphere harbors new, as-yet-undiscovered paradigms for biomass deconstruction, and the lessons learned from their analysis will greatly benefit biomass conversion science in the future.