This work reviews the brown-rot fungal biochemical mechanism involved in the biodegradation of lignified plant cell walls. This mechanism has been acquired as an apparent alternative to the energetically expensive apparatus of lignocellulose breakdown employed by white-rot fungi. The mechanism relies, at least in the incipient stage of decay, on the oxidative cleavage of glycosidic bonds in cellulose and hemicellulose and the oxidative modification and arrangement of lignin upon attack by highly destructive oxygen reactive species such as the hydroxyl radical generated non-enzymatically via Fenton chemistry (Fe3+ + H2O2 -> Fe2+ + center dot OH+ -OH). Modifications in the lignocellulose macrocomponents associated with this non-enzymatic attack are believed to aid in the selective, near-complete removal of polysaccharides by an incomplete cellulase suite and without causing substantial lignin removal. Utilization of this process could provide the key to making the production of biofuel and renewable chemicals from lignocellulose biomass more cost-effective and energy efficient. This review highlights the unique features of the brown-rot fungal non-enzymatic, mediated Fenton reaction mechanism, the modifications to the major plant cell wall macrocomponents, and the implications and opportunities for biomass processing for biofuels and chemicals.