Clodronate (CLO) is a bisphosphonate (BP) with proved efficacy in the treatment of osteoporosis. The reason of its activity is the anti-resorptive action, which is a common characteristic of BPs. Contrary to other BPs, CLO has a relatively low affinity for bone and a peculiar mechanism of action. CLO is effective in several diseases associated to excessive bone resorption as bone Pagets disease and CRPS type I. Moreover, there are data showing activity of CLO in the erosive osteoarthritis of the hands, in the osteoarthritis of the knees, in the treatment of extra-articular calcifications and in preventing the mobilization of knee and hip prosthesis.