Production of biomass from native prairie species offers the opportunity to produce energy and chemicals while providing substantial ecological services in the Northern Great Plains. This paper analyzes the application of rapid pyrolysis to produce bio-oil, which has the potential for use as a low-grade fuel oil or as a source for extraction of valuable chemicals. Yields of bio-oil, the quantities of extractable chemicals, and chemical prices drive the economics of this concept, which has a more extensive track record utilizing wood chips. A spreadsheet model was developed to determine gross margins available to defray costs to extract and refine such chemical products as hydroxyacetaldehyde, phenol, formic acid, acetic acid and various resins. Although efforts to hydrolyze anhydroglucose were successful, efforts to produce ethanol from the resulting six-carbon sugars were unsuccessful in a related trial. To understand the overall project economics, it was necessary to consider the availability and productivity of lands in the Northern Great Plains that can provide low cost native prairie grasses including Big Bluestem and Switchgrass. Production economics and transportation economics were analyzed to determine the costs of native prairie grasses delivered to a plant capable of pyrolyzing the biomass. Competing technologies that could also use native prairie grasses are considered as well as policy alternatives important for production of energy and chemicals from native prairie grasses.