The biogeochemical liabilities of grain-based crop production for bioenergy are no different from those of grain-based food production: excessive nitrate leakage, soil carbon and phosphorus loss, nitrous oxide production, and attenuated methane uptake. Contingent problems are well known, increasingly well documented, and recalcitrant: freshwater and coastal marine eutrophication, groundwater pollution, soil organic matter loss, and a warming atmosphere. The conversion of marginal lands not now farmed to annual grain production, including the repatriation of Conservation Reserve Program (CRP) and other conservation set-aside lands, will further exacerbate the biogeochemical imbalance of these landscapes, as could pressure to further simplify crop rotations. The expected emergence of biorefinery and combustion facilities that accept cellulosic materials offers an alternative outcome: agricultural landscapes that accumulate soil carbon, that conserve nitrogen and phosphorus, and that emit relatively small amounts of nitrous oxide to the atmosphere. Fields in these landscapes are planted to perennial crops that require less fertilizer, that retain sediments and nutrients that could otherwise be transported to groundwater and streams, and that accumulate carbon in both soil organic matter and roots. If mixed-species assemblages, they additionally provide biodiversity services. Biogeochemical responses of these systems fall chiefly into two areas: carbon neutrality and water and nutrient conservation. Fluxes must be measured and understood in proposed cropping systems sufficient to inform models that will predict biogeochemical behavior at field, landscape, and regional scales. Because tradeoffs are inherent to these systems, a systems approach is imperative, and because potential biofuel cropping systems and their environmental contexts are complex and cannot be exhaustively tested, modeling will be instructive. Modeling alternative biofuel cropping systems converted from different starting points, for example, suggests that converting CRP to corn ethanol production under conventional tillage results in substantially increased net greenhouse gas (GHG) emissions that can be only partly mitigated with no-till management. Alternatively, conversion of existing cropland or prairie to switchgrass production results in a net GHG sink. Outcomes and policy must be informed by science that adequately quantifies the true biogeochemical costs and advantages of alternative systems.