Osteoporosis is a "silent" disease and the patient has usually no clue of it until the occurrence of a fragility fracture. Prevention requires a continuous daily treatment that could be uncomfortable to the patient. Besides the recently introduced weekly oral schedules, injectable bisphosphonates have often been used as an off-label option to ameliorate compliance. In general, although with different efficiency, almost all injectable bisphosphonates can improve bone mineral density and suppress bone resorption markers. The effect of intravenous infusions of bisphosphonates are, to a large extent, similar to equivalent intramuscular administrations, but doses and dosing intervals represent the critical issues. Pain at the injection site and acute phase reactions are relatively common to intramuscular clodronate and intravenous infusions of nitrogen-containing bisphosphonates, respectively. Under certain circumstances, intermittent treatment with injectable bisphosphonates might represent a feasible alternative when compliance is at risk.