Orthophosphate (H2PO4 −, Pi) is an essential macronutrient required for many fundamental processes in plants, including photosynthesis and respiration, as well as nucleic acid, protein, and membrane phospholipid synthesis. The immense use of Pi-containing fertilizers in agriculture demonstrates how the soluble Pi levels of most soils are suboptimal for crop growth. The aim of this review is to explore recent and exciting advances concerning our understanding of adaptive metabolic processes that plants have evolved to alleviate the negative impact of nutritional Pi deficiency. Plant Pi starvation responses arise from complex signaling pathways that integrate altered gene expression with post-transcriptional and post-translational mechanisms. The resultant remodeling of the transcriptome, proteome, and metabolome enhances the efficiency of root Pi acquisition from the soil, as well as the use of assimilated Pi throughout the plant. We emphasize how the upregulation of high affinity Pi transporters and intra- and extracellular Pi scavenging and recycling enzymes, organic acid anion efflux, membrane remodeling, and the remarkable flexibility of plant metabolism and bioenergetics contribute to the survival of Pi-deficient plants. This research field is enabling development of a broad range of innovative and promising strategies for engineering P-efficient crops. Such cultivars are urgently needed to reduce inputs of unsustainable and nonrenewable Pi fertilizers for maximum agronomic benefit, and long-term global food security and ecosystem preservation.