The immune system has effectively evolved to protect the host against foreign invaders, including bacterial, viral, and parasitic infiltrates. Less clear has been the interaction and the protective effects the immune system mounts against its own infiltrates: cancer cells. Here we consider the dynamic interactions between cancer and the associated host immune response by highlighting the key players involved in engaging an effective antitumor immune response and the mechanisms responsible for enabling the evolution of cancer cells to escape immunosurveillance. By developing an appreciation for the dual function of the immune system in the setting of cancer biology, we also consider the clever strategies that have been employed to uncover tumor targets, including tumor-associated antigens and the mechanisms for enhancing or reengaging the immune system to mount an effective antitumor immune response. Finally, we incorporate these key findings into the context of immunotherapy, a rapidly evolving field aimed at combating tumor escape by enabling the host immune system to regain its tumor-eradicating functions. This review contains 5 figures, 9 tables and 60 references Key words: adoptive T cell therapy, checkpoint inhibitors, cytokine therapy, immunotherapy, neutralizing antibodies, tumor immunity, tumor microenvironment, vaccines