Phosphorus (P) is an essential macronutrient for all living organisms. Importantly, plants require a large amount of P to grow, and P deficiency causes huge losses in plant production. Although this issue can be mitigated by the appropriate use of phosphate (Pi) rock-derived P fertilizers, phosphate rock is a finite natural resource. Moreover, the increased demand for food as a result of our growing global population is another factor contributing to a prospective P crisis. While creating crops that are resilient to Pi deficiency presents great scientific challenge, the current progress in our understanding of how plants regulate Pi homeostasis offers some opportunities for further study. In this review, we present the published research supporting these opportunities, which are based on the molecular mechanisms that plants have evolved to respond to P deficiency. First, we focus on recent advances in P sensing and signaling pathways in the regulation of root system architecture. Next, we describe the mechanisms that regulate Pi transport and accumulation, in a Pi- (or other nutrient) dependent manner. Integrating these data will help to design an innovative strategy for improving Pi nutrition in plants. In addition, this will help with Pi scarcity, one of the challenges facing agriculture in the twenty first century.