Cellulose, the world’s most abundant organic material, is central to the world’s ecosystem. This energy resource is mobilized and recycled by microbial action. The inspired microbe has developed both considerable insight and efficient strategies for optimizing the use of this energy resource. Thus, cellulase is produced under strict regulatory control, is located optimally with respect to the microbe’s habitat, and furthermore, the enzyme components act cooperatively in a synergistic manner. This microbial genius has been integrated into the Fuels from Biomass Programs and is illustrated with examples of cellulase production from Microbispora bispora, Thermotoga neapolitana, and Trichoderma reesei.