Bisphosphonates were originally synthesized in the 19th century and used in industry for their antiscaling and anticorrosive properties. In the late 1960s their potential to treat diseases related to the metabolism of the bones became evident. The first generation of bisphosphonates included etidronic acid and clodronic acid which were introduced in the 1970s and 1980s. They were the first bisphosphonate drugs to be used successfully in the clinic. They have since then been developed further with the intention to make them more potent, enhance their distribution inside the bone and extend the duration of action. This has made it possible to give zoledronate, the most recent bisphosphonate drug to be placed on the market, in a single annual dose by intravenous infusion.