The concept, science, and technology of biofuels has captured the public's imagination as well as the attention of the academic and industrial R&D communities over the last 10 years. The 2006 US DOE report has been the basis for funding three US Bioenergy Centers, and has precipitated increased research funding worldwide. Despite the large funding resources, there is little evidence to support that processes for advanced biofuels (i.e., fuel molecules more dense than ethanol) are anywhere near achieving economic feasibility. In assessing the current status of the field for biology-based processes, there has been tremendous progress in metabolic and pathway engineering and the development of synthetic-biology tools that can be applied to engineer strains. However, the economic feasibility of what is currently possible remains in doubt, especially in light of the recent low prices of oil and natural gas. Issues liming the economic feasibility are assessed and strategies to take advantage of the successful achievements are suggested. Analysis suggests that for biofuel molecules larger than four carbons, purely biological processes cannot be currently justified, but hybrid biological/catalytic technologies may offer the necessary economies to produce such biofuels.