Growing biofuel mandates pose considerable challenges to the infrastructure needed across all stages of the supply chain − from crop production, feedstock harvesting, storage, transportation, and processing to biofuel distribution and use. This chapter focuses on the biofuel transportation and distribution network infrastructure, using Illinois as a case study. Building on an optimal land use allocation model for feedstock production, a mathematical programming model is used to determine optimal locations and capacities of biorefineries, delivery of bioenergy crops to biorefineries, and processing and distribution of ethanol and co-products (DDGS). The model aims to minimize total system costs in a multiyear planning horizon for the period of 2007–2022. Certain locations may be more suitable for corn and corn stover-based ethanol plants, others more for producing ethanol using perennial grasses (miscanthus)