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Resistance to chemotherapy in advanced cancer patients is a pressing problem. Despite a sharp surge in novel anti-cancer drugs, complete clinical response to chemotherapy is very rare and the onset of resistance is almost always the rule. Previously, we have studied the effects of the tumor microenvironment on the innate, up-front resistance to chemotherapy, demonstrating that normal (non-cancer) cells inside tumors can render cancer cells resistant to chemotherapy. In the last couple of years we have extended our work to study the role that bacteria in the tumor microenvironment might have on chemoresistance. As a first step we have characterized the bacteria in hundreds of human tumor samples representing many common tumor types including breast cancer, lung cancer, melanoma, pancreatic cancer, ovarian cancer and colorectal cancer. We then used in-vitro and in-vivo models to test for the effects of these bacteria on chemoresistance and dissected the molecular mechanisms that underlie these effects. Our result point to a potential role of intra tumor bacteria in modulating sensitivity to both conventional as well as targeted therapies and point to novel treatment directions to overcome these effects.