The periosteum covers most bone structures. It has an outer fibrous layer and an inner cambial layer that exhibits osteogenic activity. The periosteum is a dynamic structure that plays a major role in bone modeling and remodeling under normal conditions. In several disorders such as infections, benign and malignant tumors, and systemic diseases, the osteogenic potential of the periosteum is stimulated and new bone is produced. The newly formed bone added onto the surface of the cortex adopts various configurations depending on the modalities and pace of bone production. Our aim here is to describe the anatomy, histology, and physiology of the periosteum and to review the various patterns of periosteal reaction with emphasis on relations between radiological and histopathological findings. A careful evaluation of the periosteal reaction and appearance of the underlying cortex, in combination with the MRI, clinical, and laboratory data, provides valuable information on lesion duration and aggressiveness, thereby assisting in the etiological diagnosis and optimizing patient management. A solid reaction strongly suggests a benign and slow-growing process that gives the bone enough time to wall off the lesion. Single lamellar reactions occur in acute and usually benign diseases. Multilamellar reactions are associated with intermediate aggressiveness and a growth rate close to the limit of the walling-off capabilities of the bone. Spiculated, interrupted, and complex combined reactions carry the worst prognosis, as they occur in the most aggressive and fast-growing diseases: the periosteum attempts to create new bone but is overwhelmed and may be breached.