The field of biology is becoming increasingly interdisciplinary and cross-cutting. This changing research atmosphere is creating the way for a new kind of enquiry that while building upon the traditional research establishment is providing a new multidisciplinary framework to more effectively address scientific grand challenges. Using the US Department of Energy sponsored BioEnergy Science Center as an example, we highlight how impactful breakthroughs in biofuel science can be achieved within a large cross-disciplinary team environment. Such transformational insights are key to furthering our understanding and in generating models, theories and processes that can be used to overcome recalcitrance of biomass for sustainable biofuel production. Multidisciplinary approaches have an increasingly greater role to play in meeting rising demands for food, fibre, energy, clean environment and good health. Discoveries achieved by diverse minds and cross-applications of tools and analytical approaches have tremendous potential to fill existing knowledge gaps, clear roadblocks and facilitate translation of basic sciences discoveries as solutions towards addressing some of the most pressing global issues.