Osteoprotegerin (OPG) is a secreted glycoprotein central to bone turnover via its role as a decoy receptor for the receptor activator of nuclear factor kappaB ligand (RANKL) and has traditionally been linked to a number of bone-related diseases. However, there is additional evidence that OPG can promote cell survival by inhibiting TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. As a result, a number of in vitro, in vivo and clinical studies have been performed assessing the role of OPG in tumourigenesis. Similar studies have been performed regarding vascular pathologies, resulting from observations of expression and regulation of OPG in the vasculature. This review aims to provide an update on this area and assess the potential protective or detrimental role of OPG in both vascular pathologies and tumourigenesis.