Research supporting development of fully regenerative life support system of the type known as Controlled Ecological Life Support Systems or CELSS has matured to a point where a shift in approach is appropriate. The approach of environmental manipulation and observation of resulting effects on biomass production provided the bases of CELSS feasibility. While plants provide the only known method of producing food, the processes of transpiration, leading to potable water production, and assimilation, leading to CO2 uptake and O2 production, are dynamic and can be independently controlled. These processes have traditionally been considered as fixed to a particular set of growing conditions. Knowledge of these independent control parameters can provide optimization of biomass, water, and O2/CO2 process rates, increase energy efficiency, and increase stability and predictability for life support systems.Recovery of resources from waste streams is essential for future implementation and reliance on a regenerative life support system. The culture of plants in controlled environment research has traditionally utilized high quality water, nutrient, and gaseous input resources. Initial efforts to define waste stream toxicity and determine the suitability of recovered resources following processing by candidate waste treatment technologies are summarized. While there are many issues to be addressed to ensure adequate recovery and long-term management of recovered resources, there is clear indication that maintenance of predictable levels of crop performance is feasible while relying of waste derived inputs. Only in the case of CO2 recovery was the product of a single waste treatment process, incineration of inedible biomass, lead result in a toxic response. The products of biological and physical/chemical waste water processing and incineration of biomass yielded recovered water and nutrient products with no apparent toxicity to crops.The combination of technological capability with earth-based application such as the CELSS Antarctic Analog Project (CAAP) can provide the heritage necessary to mitigate risk and demonstrate the ability to provide fully regenerative life support systems for future exploration of space.