Zoledronic acid effectively reduces/delays skeletal-related events in patients with metastatic disease or skeletal-related cancers. Emerging data suggest that zoledronic acid may also exhibit anticancer properties. Zoledronic acid ± anticancer therapies in animal models inhibits soft-tissue tumor growth, decreases tumor cell proliferation, increases apoptosis, inhibits angiogenesis, alters tumor-associated macrophage function, and enhances immune surveillance. Data from in vitro and pilot studies suggest that zoledronic acid inhibits tumor cell dissemination in bone marrow, and early clinical data show that it may improve disease-related outcomes. Ongoing studies will further elucidate the role of zoledronic acid in cancer patients.