Successful active immunotherapy is expected to be specific and nontoxic. Until now, the success of immunotherapy in cancer has been sporadic and unpredictable. This has been attributable in part to the lack of a full understanding of the mechanistic underpinnings of immune regulation. Furthermore, the lack of systematic success of immunotherapy, as argued in this review, stems from failing to effectively target tumors such as non-small cell lung cancer. In this review, the rationale and design for induction of immunity to non-small cell lung cancer and clinical trials of the most important lung cancer vaccines in development are discussed.