Chlamydia pneumoniae is an obligate intracellular Gram-negative bacterium that causes persistent infections with a tendency to chronicize, which might motivate the resistance of chlamydiae to some commonly used antibiotics. The bisphosphonates are an emerging class of drugs mostly used in the palliative care of cancer patients to inhibit proliferation and metastasis of cancer cells but their role in modulating immune responses remains unknown. We investigated the in vitro activity of a highly potent bisphosphonate, zoledronic acid, on the cytotoxic effects of C. pneumoniae in human SaOS-2 osteoblast-like cells and the consequent immune response carried out by this cell line. We have reported that zoledronic acid showed a significant anti-proliferative effect on SaOS-2 cell line infected by C. pneumoniae in a time- and dose-dependent manner. We have also found that zoledronic acid induced growth inhibition of C. pneumoniae. Our data showed that C. pneumoniae-infection of SaOS-2 cells induced a significant gene expression of proinflammatory cytokines TNF-α, IL-6, IL-8 and IL-12, detected by RT-PCR, and confirmed by protein release assay. Our results demonstrated that zoledronic acid could facilitate C. pneumoniae-mediated immune response, thus reprofiling this traditional anti-tumor drug as a novel immune regulator in promoting host defense against C. pneumoniae infection.