Biocatalysts are an attractive alternative to conventional noble metal catalysts for fuel cell cathodes. In principle, they combine the possibility of more efficient operation (lower intrinsic overpotential) with the benefits of renewability, selectivity and low temperature operation. In order for these benefits to be realized in a practical cathode design, however, both improved sources of suitable oxygen-reducing oxidoreductases, and improved electrode designs are required. In this paper, we discuss the preparation and performance of cathodes based on the “encapsulation” of a laccase enzyme with silica or organic polymer binders on porous carbon paper supports. We show that these electrodes are both electrochemically efficient and stable to leaching or degradation over millions of turnovers. We also show that these electrodes can be used with conventional Pt-based anodes in a direct methanol fuel cell structure.