Meeting human needs within the ecological limits of our planet calls for continuous reflection on, and redesigning of, agricultural technologies and practices. Such technologies include fertilisers, the discovery and use of which have been one of the key factors for increasing crop yield, agricultural productivity and food security. Fertiliser use comes, however, at an environmental cost, and fertilisers have also not been a very economically effective production factor to lift many poor farmers out of poverty, especially in African countries where application on poor soils of unbalanced compositions of nutrients in fertilisers has shown limited impact on yield increase. Agronomic practices to apply existing mineral fertilisers, primarily containing N, P and K, at the right time, the right place, in the right amount, and of the right composition can improve the use efficiency of fertilisers. However, the overall progress to reduce the negative side effects is inadequate for the desired transformation toward sustainable agriculture in poor countries. Globally, there have been no fundamental reflections about the role and functioning of mineral fertilisers over the past 5 decades or more, and compared to other sectors, dismal investments have been made in mineral fertiliser research and development (R&D). In this paper, we reflect on current fertilisers and propose a more deliberate adoption of knowledge of plant physiological processes—including the diversity of mineral nutrient uptake mechanisms, their translocation and metabolism—as an entry point in identifying the physicochemical “packaging” of nutrients, their composition, amount and timing of application to meet plant physiological needs for improved instantaneous uptake. In addition to delivery through the root, we suggest that efforts be redoubled with several other uptake avenues, which as of now are at best haphazard, for the delivery of nutrients to the plant, including above ground parts and seed coating. Furthermore, ecological processes, including nutrient-specific interactions in plant and soil, plant-microorganism symbiosis, and nanotechnology, have to be exploited to enhance nutrient uptake. It is hoped that concerted R&D efforts will be pursued to achieve these strategies.