Current U.S. plans for energy security rely on converting large areas of cropland from food to biofuel production. Additionally, lands currently considered too marginal for intensive food production may be considered suitable for biofuel production; predominant cropping systems may shift to more varied arrays including novel species for which little agronomic and environmental data exist. U.S. agriculture has extensive experience with intensive corn production and much recent discussion on energy from plants has focused on simply repurposing the existing farming systems towards ethanol instead of or in addition to animal feed. Both the grain and the stover can be used in energy production, but removing the majority of the aboveground biomass from a farm field may negatively impact air, soil, and water quality. Herbaceous perennials including novel species such as Miscanthus imported from Europe and low-input native systems may offer key advantages over maize production. Farmers can use existing farm equipment and these systems are expected to require far fewer energy and financial inputs than annual row crops. However, at present, research on N and C cycling in these candidate biomass systems is fragmented and incomplete, a critical barrier to profitable and environmentally benign on-farm implementation of the U.S. biofuel agenda. In the crop production component of life cycle analyses (LCAs), nutrient (especially N) use efficiency (NUE) has been identified as a key advantage of herbaceous perennials when compared to corn. Yet true comparative data on NUE and system N balance remain sparse and there are several critical N balance determinants that are easily overlooked when LCAs are developed and when crop improvement efforts are conceived. This presentation will focus on key unknowns in nutrient use and fertilizer management for candidate biofuel cropping systems, and the potential for biotechnology solutions to improve nutrient use efficiency with a concomitant reduction in environmental impact.