Bisphosphonates provide clear anti-fracture efficacy by suppressing bone turnover. The effects of turnover suppression extend beyond slowing the rate of bone loss to changing the properties of the bone matrix. The goal of this review is to summarize the effects of bisphosphonates on material-level properties of bone, including tissue mineralization, microdamage, and the organic matrix (e.g., collagen cross-linking). The mechanical implication of these changes is also addressed. Because of a reduction in turnover that increases the mean tissue age, bisphosphonates increase the mean degree and homogeneity of mineralization, the accumulation of microdamage, and the degree of both enzymatic and non-enzymatic collagen cross-linking. These changes combine to reduce the energy absorption capacity (material-level toughness) without altering the material-level strength or modulus of the tissue. The implication of these material-level changes remains unclear, as the reduced rate of bone loss, together with the improvement in bone mineral density and the maintenance of trabecular architecture, appears sufficient to reduce fracture risk. Continued study of the changes in material-level properties with bisphosphonate treatment is warranted. With treatment duration now extending into its second decade in some patients, it remains possible that over time the changes in material-level properties could override the structural-level benefits.