Catalytic processes for biomass conversion are currently gaining renewed importance as potential alternatives to petrochemical counterparts. The metal-catalyzed hydrogenolysis of cellulose and sugars presents an interesting approach for the synthesis of fuels and polyols. This chapter covers the historical development of the hydrogenolysis of cellulose, discusses the mechanistic understanding of the reaction and highlights recent advances concerning catalyst development and process optimization. More specifically, the hydrolysis of cellulose and the degradation of glucose in aqueous medium as well as the role of the hydrogenation/hydrogenolysis catalyst are discussed to provide an insight into factors governing product distribution. Studies focusing on cellobiose as a model compound of cellulose are covered. Finally, an overview of recently developed catalyst systems based on noble and base metals in neutral and acidic aqueous medium is given. These studies confirm that the hydrogenolysis of cellulose is a highly versatile reaction allowing for optimization of the product distribution either towards hexitols or towards shorter-chain polyols, such as ethylene and propylene glycol.