Paget's disease of bone is a focal bone disorder that is common among older people of Western European descent. It is an unusual disorder, for although we now have safe and highly effective treatment, there are many aspects of its pathogenesis and natural history that we do not yet understand. Recent years have seen significant advances in the understanding of its epidemiology, genetics and molecular biology, but an integrated view that incorporates all these aspects remains elusive. In this review we examine some of the outstanding problems, the solutions to which seem likely to change our understanding of bone cell biology.