Despite advances in surgical chemotherapeutic and radiotherapeutic techniques, the overall cure rates for head and neck cancer have been disappointing. There is experimental and clinical evidence that deficiencies in the immune system play an important role in the initiation and propagation of cancer. Several strategies have been investigated to try to correct these deficiencies and also to improve the immune response. This article reviews proposed mechanisms of immunosuppression, techniques in nonspecific immunotherapy, use of tumor-infiltrating and cytokine-activated lymphocytes, discoveries and potential uses of tumor antigens, and advances in immunogene therapy in head and neck cancer. These mechanisms of immunotherapy may become an important modality in the treatment of head and neck cancer.