Diphosphonates are among the many commonly prescribed drugs for osteoporosis management. These synthetic analogues of physiologically occurring inorganic pyrophosphate bind to the hydroxyapatite crystals of bone. Diphosphonates act by decreasing the amount of osteoclast-mediated bone resorption by inducing apoptosis and disrupting the mevalonate biosynthetic pathway. Prospective clinical trials have shown that diphosphonates increase bone mineral density and reduce the risk of fracture. Diphosphonates are generally well tolerated, with a low incidence of side effects. They may be administered orally or intravenously; infusions are the most potent. Few studies have directly studied the effect of diphosphonates on the rate of fracture or time to union. Concern exists regarding the long-term safety of diphosphonates, particularly in patients with osteoporosis. New evidence suggests that long-term therapy may increase the risk of fracture of the femoral shaft, with possible morphologic and prodromal warning signs. Further prospective research into the consequences of diphosphonate-mediated suppressed bone turnover is needed to elucidate a safe duration of treatment.