Glioma is the most frequently occurring brain tumor, but the prognosis of patients with gliomas remains poor despite advances in surgery, radiotherapy, and chemotherapy. Therefore, great efforts have been made to develop improved therapeutic strategies. Cytokines are a heterogeneous group of soluble small polypeptides or glycoproteins that exert pleiotropic and redundant effects that promote the growth, differentiation, and activation of normal cells. Cytokines have either pro- or anti-inflammatory activity and immunosuppressive activity, depending on the microenvironment surrounding the tumor. The microenvironment consists of heterogeneous tumor cells, immune cells, and extracellular matrix. Modulation of the microenvironment by the tumor is essential for its growth and progress. Cytokine production acts as a means of communication in the tumor microenvironment. In this article, we review the cross-talk between cytokines in the tumor microenvironment and the cytokine therapies that have been used till date for glioma treatment.