Traditionally, non-small-cell lung cancer (NSCLC) is not thought of as an immunosensitive malignancy. However, recent clinical results with GVAX, a granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced autologous tumor vaccine, may suggest otherwise. This review summarizes immune-induced activity caused by GM-CSF protein and GM-CSF gene-transfected vaccines. Initial indication of use for GM-CSF protein (sargramostim) was to improve neutrophil recovery following cytotoxic chemotherapy. However, several trials involving patients with hematologic malignancy demonstrated improvement in survival related to delayed disease progression in patients receiving sargramostim in combination with chemotherapy. Subsequently, others explored potential antitumor activity with sargramostim in a variety of trials. Results did not consistently demonstrate sufficient antitumor activity to justify routine use of sargramostim as an anticancer agent. Preclinical work with GM-CSF gene-transfected vaccines, however, did demonstrate significant activity, thereby justifying clinical investigation. Patients with metastatic NSCLC who had previously failed chemotherapy demonstrated response to GVAX (3 of 33 complete responses) and dose-related improvement in survival (471 days vs. 174 days).