In nature, white-rot fungi and some bacteria secrete powerful oxidative enzymes such as peroxidases and laccases to break down lignin and lignin products. These enzymes, together with different chemical mediators, form a chemo-enzymatic system for delignifying biomass so that the microbes can gain access to the polysaccharides. Ligninolytic oxidoreductases have been widely studied in terms of their unique reaction mechanisms and industrial applicability (largely related to production and stability issues). In the context of an integrated biorefinery, both ligninolytic organisms and ligninolytic enzymes may have a role to play for delignification and lignin valorization. This chapter reviews microbial degradation of lignin from an enzymatic perspective, discusses the recent discoveries and advances in a global context including genomic and structure/function information, and provides a perspective on the potential for its utilization in different green chemistry transformations.