After fifty years of experience with several generations of bisphosphonates (BPs), and 25 years after these drugs were approved for use in humans, their mechanical effects on bone are still not fully understood. Certainly, these drugs have transformed the treatment of osteoporosis in both men and women. There is no question that they do prevent fractures related to low bone mass, and there is widespread agreement that they increase strength and stiffness of the vertebrae. There is less consensus, however, about their effects on cortical bone, or on bone tissue properties in either trabecular or cortical bone, or their effects with longer periods of treatment. The consensus of most studies, both those based on ovariectomized and intact animal models and on testing of human bone, is that long-term treatment and/or high doses with certain BPs make the bone tissue more brittle and less tough. This translates into reduced energy to fracture and potentially a shorter bone fatigue life. Many studies have been done, but Interpretation of the results of these studies is complicated by variations in which BP is used, the animal model used, dose, duration, and methods of testing. Duration effects and effects on impact properties of bone are gaps that should be filled with additional testing.