Referee: Dr. Charles A. S. Hall, Department of Environmental Studies, State University of New York, College of Environmental Science and Forestry, 1 Forestry Drive, Syracuse, NY 13210 Biofuel production systems are sometimes claimed to be able to fill in for future fossil fuel shortages as well as to decrease carbon dioxide emissions and global warming. As such, they are often promoted as a “green” alternative to fossil fuels. I present a comprehensive, system-based case study of biofuel production from maize or corn (Zea mays L.) and evaluate it critically in this review. The case study is taken as an example of the comprehensive approach that I suggest for any energy crop. I conclude that the biofuel option on a large scale is not a viable alternative based on economic, energy and eMergy (amount of available energy [exergy] of one form [usually solar] that is directly or indirectly required to provide a given flow or storage of exergy or matter) analyses of the case study data and estimated possible improvement of yield and efficiency. This is true for developed countries due to their huge energy demand compared with what biofuel options are able to supply as well as for developing countries due to the low yield of their agriculture and competition for land and water for food production. However, biofuels may contribute to optimizing the energy and resource balance of agricultural, livestock, or industrial production systems at an appropriate scale. I present a proposal to integrate ethanol production with industrial activities within a “zero emission framework” as a suggestion for optimization strategies capable of making the biofuel option more sustainable and profitable in those cases where it is appropriate.