Perennial cropping systems may achieve significant improvement over annual systems in the synchrony between crop nutrient demands and nutrient supplies. Improvements in nutrient synchrony would result in the reduction of nutrient losses and their associated environmental impacts. A perennial system with high levels of synchrony would also require fewer nutrient inputs, such that it may be possible to develop an agriculture that functions mostly, if not entirely, on nutrient inputs from endogenous sources (i.e., weathering of primary and secondary minerals and biological nitrogen fixation). In this paper I describe three realms of research that will inform the development of relatively high-yielding grain production systems grown on endogenous nutrient supplies: (1) improvement of nutrient synchrony through the development of perennial crops; (2) identification of soils that are in a high nutrient release phase of pedogenesis, which could balance the export of rock-derived nutrients in crop harvests; and (3) optimization of legume density, harvest index and percent nitrogen derived from the atmosphere (%Ndfa) to achieve adequate nitrogen inputs through biological fixation.