This chapter provides a background for consideration of the sustainability of biofuels in Latin America and the Caribbean (LAC). Facing the twin problems of increasingly scarce and risky petroleum resources and global climate change, many nations are turning to biofuels for the transportation sector. For several decades, the world leaders in biofuels production and use have been, by far, Brazil and most recently the USA. These programs have been considered to be in the national interest, and have been subsidized by governments to varying degrees until more recently. However, the sustainability of biofuels production has come under serious challenge, including their effect on greenhouse gas emissions, biodiversity, deforestation, water use and pollution, food security, labor practices, among other issues. The first generation of biofuels in LAC has relied upon feedstocks that are food based, primarily sugarcane and soybeans, and conversion to non-food-based, second-generation biofuels has been extremely slow. An overview will be provided of numerous sustainability concerns, challenges, and policy responses, including nongovernmental organization governance and certification standards and schemes for biofuel and feedstock production. Given the already large export markets for US and Brazilian ethanol, and for Argentinean biodiesel, greater coordination between national biofuels sustainability programs will be essential to their successful implementation.