Cortical bone is a kind of natural biological composite materials, which is mainly composed of tropocollagen molecules and nanoscale hydroxyapatite mineral crystals. It possesses high strength, stiffness and fracture toughness and has the ability to tolerate damage and self-heal. In the long process of evolution, bone tissues form the biomechanical strength and toughness to meet its functional needs. The excellent mechanical properties of cortical bone are closely related to its hierarchical microstructure. This paper reviewed the hierarchical microstructure of cortical bone and its toughening mechanisms, which would contribute to understanding the diagnosis, prevention and treatment of aging-related osteoporosis and the pathological mechanism of bone diseases.