A primary objective of current U.S. biofuel law – the “Energy Independence and Security Act of 2007” (EISA) – is to reduce dependence on imported oil, but the law also requires biofuels to meet carbon emission reduction thresholds relative to petroleum fuels. EISA created a renewable fuel standard with annual targets for U.S. biofuel use that climb gradually from 9 billion gallons per year in 2008 to 36 billion gallons (or about 136 billion liters) of biofuels per year by 2022. The most controversial aspects of U.S. biofuel policy have centered on the global social and environmental implications of land use. In particular, there is an ongoing debate about whether “indirect land use change” (ILUC) would cause biofuels to become a net source, rather than sink, of carbon emissions. Estimates of ILUC induced by biofuel production can only be inferred through modeling. This paper evaluates how model structure, underlying assumptions, and the representation of policy instruments influence the results of U.S. biofuel policy simulations. The analysis shows that differences in these factors can lead to divergent model estimates of land use and economic effects. Model estimates of the net conversion of forests and grasslands induced by U.S. biofuel policy range from 0.09 ha/1000 gallons described in this paper to 0.73 ha/1000 gallons from early studies in the ILUC change debate. We note that several important factors governing LUC change remain to be examined. Challenges that must be addressed to improve global land use change modeling are highlighted.