Rapid growth in demand for lignocellulosic bioenergy will require major changes in supply chain infrastructure. Even with densification and preprocessing, transport volumes by mid-century are likely to exceed the combined capacity of current agricultural and energy supply chains, including grain, petroleum, and coal. Efficient supply chains can be achieved through decentralized conversion processes that facilitate local sourcing, satellite preprocessing and densification for long-distance transport, and business models that reward biomass growers both nearby and afar. Integrated systems that are cost-effective and energy-efficient will require new ways of thinking about agriculture, energy infrastructure, and rural economic development. Implementing these integrated systems will require innovation and investment in novel technologies, efficient value chains, and socioeconomic and policy frameworks; all are needed to support an expanded biofuels infrastructure that can meet the challenges of scale.