Sugarcane (a complex hybrid of Saccharum spp.) has high biomass and sucrose accumulation in its stem, making it a favourable feedstock for bioenergy production. This chapter reviews the key issues and challenges faced when expanding sugarcane cultivation for bioenergy, namely, competition with food crops, loss of biodiversity, potential increase in pest problems, water, air and soil pollution, yield maximization, susceptibility to drought and cold, and the issues posed by sugarcane’s complex genome. We discuss how these issues are being addressed through research into genetic improvement, improved understanding of agronomics and improved pest management practices. Case studies from Brazil and the United States offer a brief overview of sugarcane development for energy production in these two countries.