<p>Phosphate bioactive glasses (PBGs) have become widely recognized as next-generation biomaterials because of their controllable degradation behaviour, compositional flexibility, and excellent biological compatibility. Unlike silicate and borate bioactive glasses, PBGs exhibit fully controllable and congruent dissolution behaviour, enabling precise regulation of ion release and complete degradation within clinically relevant timeframes. This review presents a detailed examination of the structural chemistry, synthesis strategies, and bioactivity mechanisms of PBGs, with particular emphasis on the influence of network connectivity, modifier oxides, and dopants on their physicochemical and biological properties. The mechanistic pathway of apatite formation is discussed in detail, highlighting ionic exchange reactions, and the subsequent development of hydroxycarbonate apatite (HCA) during in vitro and in vivo evaluations. Various synthesis methods including melt-quenching, sol–gel processing, flame synthesis, and microwave assisted methods are reviewed with respect to their effects on glass homogeneity, degradation kinetics, and bioactivity. Interactions between PBGs and biological environments are reviewed through in vitro and in vivo studies, focusing on hydroxycarbonate apatite formation, cellular responses, and tissue integration. The influence of therapeutic ion doping including Ti, Zn, Fe, Cu, and Mg on structural modification and biological performance is also discussed. Collectively, this review consolidates current knowledge on phosphate-based bioactive glasses, identifies emerging research trends, and outlines key challenges and opportunities for their optimized design and future clinical translation.</p>