Toughness is a quantitative measure of bone quality in terms of its susceptibility to fracture. Thus, to elucidate the underlying mechanisms of age-related bone fractures, it is necessary to understand age-related changes in the toughness of bone. The objective of this review is to provide current understanding on the structure–function relationships of cortical bone and its correlation with the toughness of the tissue from the perspective of basic engineering principles. The review is written for the readers in the musculoskeletal research field, who may not have a strong engineering background. For better understanding of toughening mechanisms, this review intends to focus on correlations of the toughness of cortical bone with its constituents and microstructural characteristics. In addition, a special emphasis is placed on age-related changes in the toughness of bone.