Aneurysmal bone cysts (ABCs) are uncommon lesions that involve the axial and appendicular bones. Although biologically benign, ABCs have the tendency to assume an aggressive behavior causing local destruction of the underlying bone and neighboring soft tissues. Morphologically, ABCs are composed of cyst-like cavities filled with blood and bounded by an array of diverse cells including fibroblasts, inflammatory infiltrates and osteoclast-like multinucleated giant cells. From a molecular perspective, the osteoclast-like multinucleated giant cells harbor high expression of receptor activator of nuclear factor kappa B (RANK) receptors, whereas the neoplastic stromal cells harbor high expression of RANK ligand (RANKL). The RANK-RANKL interaction has been implicated in the carcinogenesis of ABCs and giant cell tumor of bones (GCTBs). Currently, the optimal management of ABCs remains a hotly debated topic. There are a multitude of treatment modalities (that is, surgery, sclerotherapy, radiotherapy and selective arterial embolization), and each modality has its own benefits, morbidity and risk of complications. The local aggressiveness of ABC and its high rates of relapse following treatment has demanded the march towards discovering more innovative therapies. One of such therapies is denosumab, a monoclonal antibody targeted against the RANKL. Denosumab is already approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is unamenable to surgery, or initial surgery is anticipated to result in significant morbidity. However, denosumab is not approved by the FDA for the management of ABCs. However, taking into consideration the morphological similarity between GCTBs and ABCs, some treating physicians have logically opted to use denosumab in an off-label manner to treat select ABCs. To the best of knowledge, no study has attempted to summarize the related literature on the use of denosumab in ABCs. Therefore, the primary aim of this study is to narratively review all the available literature about the efficacy and safety of the use of off-label denosumab in the management of patients with ABCs.