Advanced biofuels will be developed using cellulosic feedstock rather than grain or oilseed crops that can also be used for food and feed. To be sustainable, these new agronomic production systems must be economically viable without degrading the soil and other natural resources. This review examines six agronomic factors that collectively define many of the limits and opportunities for harvesting crop residue for biofuel feedstock in the midwestern United States. The limiting factors include soil organic carbon, wind and water erosion, plant nutrient balance, soil water and temperature dynamics, soil compaction, and off-site environmental impacts. These are discussed in relationship to economic drivers associated with harvesting corn (Zea mays L.) stover as a potential cellulosic feedstock. Initial evaluations using the Revised Universal Soil Loss Equation 2.0 (RUSLE2) show that a single factor analysis based on simply meeting tolerable soil loss (T) might indicate that stover could be harvested sustainably, but the same analysis, based on maintaining soil organic carbon (SOC), shows the practice to be non-sustainable. Modifying agricultural management to include either annual or perennial cover crops is shown to meet both soil erosion and soil carbon requirements. The importance of achieving high yields and planning in a holistic manner at the landscape scale are also shown to be crucial for balancing limitations and drivers associated with renewable bioenergy production.