To date, in lung cancer, early attempts to modulate the immune system via vaccine-based therapeutics have been unsuccessful. An improved understanding of tumor immunology has facilitated the production of more sophisticated lung cancer vaccines. It is anticipated that it will likely require multiple epitopes of a diverse set of genes restricted to multiple haplotypes to generate a truly effective vaccine that is able to overcome the various immunologic escape mechanisms that tumors employ. Other issues to overcome include optimal patient selection, which adjuvant agent to use, and how to adequately monitor for an immunologic response. This review discusses the most promising vaccination strategies for non-small cell lung cancer including the allogeneic tumor cell vaccine belagenpumatucel-L, which is a mixture of 4 allogeneic non-small cell lung cancer cell lines genetically modified to secrete an antisense oligonucleotide to transforming growth factor β2 and 3 other target protein-specific vaccines designed to induce responses against melanoma-associated antigen A3, mucin 1, and epidermal growth factor.