ABSTRACTTargeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune‐based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor‐resident cell populations. Several approaches for targeting the tumor microenvironment are under development. Nanoparticles, peptide or antibody‐based delivery, and exploitation of cellular influx are all promising ways to delivery immune modulating compounds to tumors. J. Cell. Biochem. 118: 3049–3054, 2017. © 2017 Wiley Periodicals, Inc.