The development of oncoprotein-targeted anticancer drugs is an invaluable weapon in the war against cancer. However, cancers do not give up without a fight. They may develop multiple mechanisms of drug resistance, including apoptosis inhibition, drug expulsion, and increased proliferation that reduce the effectiveness of the drug. The collective work of researchers has highlighted the role of cytokines in the mechanisms of cancer drug resistance, as well as in cancer cell progression. Furthermore, recent studies have described how specific cytokines secreted by cancer stromal cells confer resistance to chemotherapeutic treatments. In order to gain a better understanding of mechanism of cancer drug resistance and a prediction of treatment outcome, it is imperative that correlations are established between global cytokine profiles and cancer drug resistance. Here we discuss the recent discoveries in this field of research and discuss their implications for the future development of effective anti-cancer medicines.