The recent boom and collapse of the corn ethanol industry calls into question on the long-term sustainability of biofuels and traditional approaches to biofuel systems design. Compared with petroleum based transportation fuel production, biofuel production systems are so closely connected and heavily influenced by natural systems that they have to deal with high degrees of complexity, variability and unpredictability. Accordingly, a fundamental change in design philosophy is necessary for long-term viability of biofuel production. The new approach requires the system to be designed not for a narrowly defined efficiency (both economic and ecological), but for resilience (indicated by characteristics such as diversity, efficiency, cohesion and adaptability) to absorb unexpected disruptions and changes. Also, biofuel systems must be endowed with transformability to allow for "creative destruction" when current transportation fuels are eventually supplanted by new vehicle technologies and/or mode of transportation. This paper addresses important concepts in the design of coupled engineering-ecological systems (i.e. resilience, adaptability and transformability) that determine future system trajectories at multiple scales. In addition, several emerging biofuel conversion technologies are examined from a resilience perspective. It is suggested that the thermo-chemical conversion technologies may be preferable for biofuel production from resilience aspect. However, multiple technologies may increase the diversity and flexibility of the entire industry. This paper calls for the development of quantitative metrics for resilience assessment (similar to life cycle assessment for environmental sustainability) of industrial system, which are critical for integrating resilience into technology development and system design.