Technical Abstract: Region-based production systems are needed to produce the feedstocks that will be turned into the biofuels required to meet Federal mandated targets. Executive and Legislative actions have put into motion significant government responses designed to advance the development and production of domestic biofuels and other biobased products. Thirty-six billion gallons of biofuels must be blended with U.S. transportation fuels by 2022. With more than 12 of the 15 billion gallons of corn grain ethanol presently being produced, careful planning for the expansion of a biomass sector must be done now because the land and financial resources required to produce the next 21 billion gallons of advanced biofuels is significant – 24 million acres of dedicated feedstock crops and $160 billion to build the needed biorefineries. This paper discusses Growing America’s Fuel, the U.S. Government strategy to increase the production of biofuels and provide new opportunities for farm, forest, and rural community economic development, and the need for sustainable biomass production supported by the development and growth of fully integrated regional systems that produce biofuels, biopower, and other biobased products. Specific attention is given to the need for understanding expanded advanced biofuel production in a context of multifunctional landscapes, addressing uncertainties of expanded production up-front, using regionalized feedstock strategies, recognizing natural biophysical realities of production limits, the need for continued production efficiency improvement, and policy dynamics. American farms and forests have the capacity to support expanded biofuels production, but care will be needed to produce biomass and other feedstocks in ways that consider the multiple economic, environmental, and social benefits that our rural lands and communities provide so that truly sustainable systems are deployed.