Lignocellulosic biofuels generated from plant cell walls are a promising alternative to gasoline. There are a large number of potential lignocellulosic feedstocks including switchgrass (Panicum virgatum L.), a high-yielding, native U.S. grass species that is widespread throughout the eastern United States. Switchgrass is suitable for growth in a range of climates, and provides many positive ecosystem services. There are two distinct genetic forms of switchgrass and our previous work demonstrated that the same optimal thermochemical pretreatment conditions could be used for each. More recently we have investigated the effect of environmental and agronomic conditions experienced during switchgrass growth on fermentation of biomass-derived sugars. We observed that both the choice of harvest date and severe drought experienced by the plants can result in different degrees of fermentation inhibition, neither of which was predictable from the biomass or hydrolysate compositions. These results show the importance of running fermentation on potential materials, not simply relying on biomass and hydrolysate characterizations, in order to identify possible sources of inhibition.