Though management of essential macronutrients, including nitrogen, phosphorous and potassium and water is crucial in any cropping system, it is of particular concern for sustaining future bioenergy crops that will be grown on sub-optimal soils lacking these essential resources. Use of fertilizers and applied irrigation will improve upon this, but at a significant increase in the net cost for energy derived from bioenergy fuels. In recent years, an increasing number of reports have appeared documenting healthy plant growth under nutrient limitation and drought conditions by applying plant growth promoting rhizobacteria (PGPB). Even so, most aspects of these unique plant-microorganism associations have been little studied at a systems-level and from a detailed mechanistic perspective. Knowledge gained from more intensive research on PGPB and their effects should increase their utility and field application in future bioenergy cropping systems. What is lacking is a genetically tractable, model system that can be employed to make more rapid progress toward understanding PGPB function. Our recent work in Setaria viridis (Pankievicz et al., The Plant Journal, 2015) using Azospirillum brasilense and Herbaspirillum seropedicae bacteria, has shown that it is a robust model C4 grass system for studying PGPB attributable to biological nitrogen fixation and other phytostimulatory actions. Leveraging several imaging approaches, including radioluminescence, optical and nanoSIMS in combination with radiotracer metabolic fluxomics and proteomics, we are beginning to get a clearer picture into the physiological and metabolic basis for plant growth promotion via these microbial associations - and with a sequenced genome for S. viridis and plant transformation efforts underway, this system promises to provide even greater insight that should help accelerate translation and deployment of new strategies for future bioenergy crop sustainability.