This chapter is devoted to the scale, scope, and specific issues confronting the cleanup and long-term disposal of the U.S. nuclear legacy generated during WWII and the Cold War Era. The research reported is aimed at complex microbiological interactions with legacy waste materials generated by past nuclear production activities in the United States. The intended purpose of this research is to identify cost effective solutions to the specific problems (stability) and environmental challenges (fate, transport, exposure) in managing and detoxifying persistent contaminant species. Specifically addressed are high level waste microbiology and bacteria inhabiting plutonium laden soils in the unsaturated subsurface.