The treatment of non-small-cell lung cancer (NSCLC) on an immunologic basis has been both welcomed and rejected in the past decades. Negative outcomes of immunotherapy studies have been commonly explained by the poor immunogenicity of tumors arising in the lungs. On the other hand, there is an overwhelming body of literature on the importance of the inflammatory and immune responses in lung carcinogenesis. Interaction between inflammatory cells and tumor cells facilitates pro-cancer processes, such as angiogenesis and tumor cell migration. In addition to these interactions, antigen-specific antitumor responses are overtly present in NSCLC. These data suggest a role for immunotherapy in the treatment of NSCLC when properly applied. Targeting the antigen-specific immune response with modern vaccines has shown promising results. In this review the inflammatory process in NSCLC is described. The relevance of the specific immune response and immunotherapy studies and potential targets for future immunotherapy are discussed.