Biofuels, such as ethanol and butanol, represent an emerging source of renewable energy. Ethanol as first generation biofuel is produced mostly from food crops, including corn and sugarcane. Our efforts toward biofuel production is linked to second generation biofuels, where cellulosic materials are converted to simple sugars for subsequent fermentation by microorganisms to biofuels. A bottleneck in the steps leading to production of biofuels from cellulosic feedstock is the inability of industrially harnessed microbes to convert recalcitrant plant biomass directly to the target biofuel. Therefore, a necessary intermediate step is to digest the cellulose to glucose either by dilute acid hydrolysis or enzymatic hydrolysis. Second generation bioenergy feedstock such as the giant grass Miscanthus and Switchgrass are composed of about 31% cellulose and 25% hemicellulose. While much emphasis has been placed on depolymerizing the cellulose in plant cell wall for biofuel production, it is obvious that strategies that also release the sugars in hemicellulose for fermentation will make second generation biofuel production more economical. Our lab has therefore been using molecular, biochemical, and biophysical approaches to study the strategies used by bacteria to degrade hemicellulose. Our studies, based on mesophilic, thermophilic, and hyperthermopilic bacteria, demonstrate that a strategy that involves secreting enzymes that remove side-chain decorations to expose the linear β(1,4)-xylosyl residues for hydrolysis abounds in nature. Fascinatingly, microorganisms have developed large sets of enzymes that incorporate multiple functional activities into single polypeptides, most likely to increase the efficiency of plant cell wall degradation. Modular architecture, biochemical and structural data will be presented to illustrate the ingenuity of plant cell wall deconstructing microbes. It is anticipated that a better understanding of the plant cell wall structure, together with clearer insights into the evolution of the enzymatic strategies employed by microbes to deconstruct storage polysaccharides, will accelerate the realization of the noble goal of converting biomass to biofuels.