Lung cancer is the leading cause of cancer deaths in the United States and throughout the world; globally, there are more than 1.1 million deaths each year. Treatment modalities currently employed are significantly limited; 50% of patients experience disease recurrence after surgery, and less than a quarter of patients respond to systemic chemotherapy. These statistics have fueled the search for a safer, more effective treatment modality. Despite significant advances in our understanding of the molecular basis of cancer immunology, many obstacles remain. However, encouraging clinical results in patients immunized with autologous tumor cell vaccines expressing granulocyte macrophage colony-stimulating factor strongly advocate further investigation of immunotherapy in non-small-cell lung cancer (NSCLC). Further studies are needed to demonstrate whether these novel therapies can potentially complement or even replace current therapeutic approaches. We present a review of the various vaccine-based strategies employed to target and treat NSCLC.