Bisphosphonates are pharmacological compounds that have been used for the prevention and treatment of several pathological conditions including osteoporosis, primary hyperparathyroidism, osteogenesis imperfecta, and other conditions characterized by bone fragility. Many studies have been performed to date to analyze their effects on inflammation and bone remodelling and related pathologies. The aim of this review is, starting from a background on inflammatory processes and bone remodelling, to give an update on the use of bisphosphonates, outlining the possible side effects and proposing new trends for the future. Starting from a brief introduction on inflammation and bone remodelling, we collect and analyze studies involving the use of bisphosphonates for treatment of inflammatory conditions and pathologies characterized by bone loss. Selected articles, including reviews, published between 1976 and 2011, were chosen from Pubmed/Medline on the basis of their content. Bisphosphonates exert a selective activity on inflammation and bone remodelling and related pathologies, which are characterized by an excess in bone resorption. They improve not only skeletal defects, but also general symptoms. Bisphosphonates have found clinical application preventing and treating osteoporosis, osteitis deformans (Paget's disease of bone), bone metastasis (with or without hypercalcaemia), multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, and other conditions that feature bone fragility. Further clinical studies involving larger cohorts are needed to optimize the dosage and length of therapy for each of these agents in each clinical field in order to be able to maximize their properties concerning modulation of inflammation and bone remodelling. In the near future, although "old" bisphosphonates will reach the end of their patent life, "new" bisphosphonates will be designed to specifically target a pathological condition.