Biofuels are widely touted as viable, albeit not straightforward, alternatives to petroleum-derived fuels. To best determine their utilization, many practitioners turn to life-cycle assessment (LCA) to ascertain the “environmental footprint”. Although parameters such as resource and land use, along with infrastructure, can be incorporated into LCA algorithms, many have noted that the methodological approach still needs careful attention. In this Feature, McKone et al. outline seven grand challenges that need to be engaged and surmounted to provide the best way forward for biofuel use.