The tumor microenvironment is a complex assortment of cells that includes a variety of leukocytes. The overall effect of the microenvironment is to support the growth of tumors and suppress immune responses. Immunotherapy is a highly promising form of cancer treatment, but its efficacy can be severely compromised by an immunosuppressive tumor microenvironment. Chemotherapy and radiation treatment can mediate tumor reduction through cytotoxic effects, but it is becoming increasingly clear that these forms of treatment can be used to modify the tumor microenvironment to liberate tumor antigens and decrease immunosuppression. Chemotherapy and radiotherapy can be used to modulate the tumor microenvironment to enhance immunotherapy. ? 2013 Landes Bioscience.