Abstract: Zoledronic acid(ZA) is the third generation of nitrogen-containing bisphosphonates and widely used in the treatment of bone disease in clinic. Previous studies have found that zoledronic acid have antitumor effect in a variety of tumor cells in vitro and in vivo. Meanwhile, it can increase the antitumor effect of its combination with chemotherapy, endocrine therapy and radiation therapy. Recent studies have found that zoledronic acid also can be coordinated to increase the antitumor effect of targeted and immunomodulatory drugs. Its antitumor mechanism includes inhibiting mevalonate pathway, influencing tumor signaling pathways, regulating immune response, anti-angiogenesis and so on. This review collects the latest information about zoledronic acid combined with targeted and immunomodulatory drugs in antitumor therapy.