Bisphosphonates are used for supportive treatment in bone metastases of malignant diseases. Advance in various therapeutic options, molecular targeted therapies of malignant diseases result in longer survival, and may bring a higher number of patients surviving until development of secondary lesions, e.g. bone metastases. This review summarizes the antitumor activity of the amino-bisphosphonate zoledronate, describing results of in vitro and animal model studies. Zoledronic acid treatment in patients with malignant solid tumors causing bone metastases prolongs their survival. According to the emerging, until now not too large amount of data, zoledronic acid may have a clinically significant and important direct antitumor activity which is resulted by many pathomechanical pathways summarized in this report. Randomized clinical trials are needed for evaluating real life antitumor activity of amino-bisphosphonates.