Energy is an integral part of society. The major US energy sources of fossil fuels (coal, oil, natural gas); biofuels (ethanol); and wind are concentrated in grassland ecosystems of the Great Plains. As energy demand continues to increase, mounting pressures will be placed on North American grassland systems. In this review, we present the ecological effects of energy development and production on grassland systems. We then identify opportunities to mitigate these effects during the planning, construction, and production phases by using informed methodology and improved technology. Primary effects during energy development include small- and large-scale soil disturbance and vegetation removal as small patches of grasslands are used to host oil or gas wells, wind turbine pads, associated roadways, and pipelines or through the conversion of large grassland areas to biofuel croplands. Direct habitat loss or habitat fragmentation can affect wildlife directly through increased mortality or indirectly through reduction in habitat quantity and quality. During energy production, air and water quality can be affected through regular emissions or unplanned spills. Energy development can also affect the economy and health of local communities. During planning, energy development and production effects can be reduced by carefully considering effects on grasslands during siting and even by selecting different energy source types. During construction, effects on soil and plant systems can be minimized by eliminating weed populations before disturbance, salvaging and stockpiling topsoil for future revegetation, and harvesting native local seed for postsite restoration. During energy production operations, noise and road traffic reduction plans and atmospheric monitoring will enable more informed mitigation measures. Continued research on energy development effects and mitigation measures is necessary to establish best management practices beneficial to grassland health while providing needed energy for the United States.