Sweet sorghum is a tall (4-6 m) grass that grows well in hot and water-limited environments and that accumulates large amounts of soluble sugars in its stem juice. Given the large amount of bagasse (crushed stems) that remains after the extraction of the juice, sweet sorghum is an ideal crop to transition from first-generation sugar-based biofuels and chemicals to second-generation biomass-based fuels and chemicals. I will focus on three approaches to improve bioenergy sorghum: 1) Enhanced resistance against the fungal disease anthracnose is critical for high yields in the Southeastern U.S. We have identified two novel resistance loci following high-throughput genotyping of a mapping population. I will discuss some of the technical considerations to streamline this process. 2) A better understanding of the enzymes involved in lignin biosynthesis can form the basis for improving the bioprocessing characteristics of the bagasse. I will share structural models that, combined with analysis of mutants, form the basis for the modification of lignin composition with minimal negative impacts on plant fitness. 3) Novel, high-value nanomaterials from the lignin-rich waste stream of the biorefinery can offset some of the operating costs of the biorefinery. Some of the nanomaterials show promise in biomedical applications. Commercial-scale application of these combined approaches is expected to lead to production of fuels and chemicals in an environmentally and economically sustainable manner.