Bone is a complex tissue of which the principal function is to resist mechanical forces and fractures. Bone strength depends not only on the quantity of bone tissue but also on the quality, which is characterized by the geometry and the shape of bones, the microarchitecture of the trabecular bones, the turnover, the mineral, and the collagen. Different determinants of bone quality are interrelated, especially the mineral and collagen, and analysis of their specific roles in bone strength is difficult. This review describes the interactions of type I collagen with the mineral and the contribution of the orientations of the collagen fibers when the bone is submitted to mechanical forces. Different processes of maturation of collagen occur in bone, which can result either from enzymatic or nonenzymatic processes. The enzymatic process involves activation of lysyl oxidase, which leads to the formation of immature and mature crosslinks that stabilize the collagen fibrils. Two type of nonenzymatic process are described in type I collagen: the formation of advanced glycation end products due to the accumulation of reducible sugars in bone tissue, and the process of racemization and isomerization in the telopeptide of the collagen. These modifications of collagen are age-related and may impair the mechanical properties of bone. To illustrate the role of the crosslinking process of collagen in bone strength, clinical disorders associated with bone collagen abnormalities and bone fragility, such as osteogenesis imperfecta and osteoporosis, are described.