Purpose of Review <p>The periosteum has long been recognized as being essential for bone growth and repair. More recently, its involvement has been observed in a range of pathological conditions, including cancer progression and invasion, premature closure of the growth plate, bone pain, pseudarthrosis, and craniosynostosis. Given that the periosteal reaction often serves as an early indicator of skeletal abnormalities, the periosteum likely plays a pivotal role at the interface of bone health and disease. In this review, recent advances in our understanding of periosteal biology are highlighted.</p> Recent Findings <p>Recent studies employing lineage tracing and genetic loss-of-function approaches have highlighted the critical role of periosteal stem cells and their progenies, as well as periosteum/perichondrium-derived factors, in both bone physiology and pathology. Crosstalk between the periosteum/perichondrium and the growth plate controls skeletal growth, and complex multicellular interactions in the periosteum underlies the pathogenesis of pseudarthrosis and craniosynostosis. The protective role of the periosteum against cancer progression has garnered attention, expanding our understanding of periosteum function.</p> Summary <p>It is now evident that the periosteum is a crucial skeletal element that is key for maintaining vertebrate homeostasis. Future research into the cellular communication in the periosteum, as well as its interactions with other skeletal elements and extra-skeletal systems, will be key to develop novel therapeutic strategies for skeletal diseases.</p>