The development of alternatives to fossil fuels as an energy source is an urgent global priority. Cellulosic biomass has the potential to contribute to meeting the demand for liquid fuel, but land-use requirements and process inefficiencies represent hurdles for large-scale deployment of biomass-to-biofuel technologies. Genomic information gathered from across the biosphere, including potential energy crops and microorganisms able to break down biomass, will be vital for improving the prospects of significant cellulosic biofuel production.