Radiolabeled bisphosphonates were developed in the 1970s for scintigraphic functional imaging of the skeleton in benign and malignant disease. Tracers such as 99mTc-methylene diphosphonate, that map focal or global changes in mineralization in the skeleton qualitatively and quantitatively, have been the backbone of nuclear medicine imaging for decades. While competing technologies are evolving, new indications and improvements in scanner hardware, in particular hybrid imaging (e.g. single photon emission computed tomography combined with computed tomography), have allowed improved diagnostic accuracy and a continued role for radiolabeled bisphosphonate imaging in current practice.