Exciting progress, in the molecular and cell biology of head and neck cancer has provided us with new ways to target cancer cells more specifically. The possibility now exists with gene therapy of targeting specific genetic defects found in certain tumor types using any one of a number of possible gene delivery systems. Although specific problems with currently existing gene therapy strategies remain to be addressed, encouraging preclinical and clinical data indicate that this is a very promising area. In addition, the exquisite sensitivity of anti/bodies directed at specific molecular targets should make antibody-conjugated toxins, radioimmunoconjugates, and antibodies alone viable therapeutic options. Finally, increased understanding of the antitumor immune response has yielded more rationally designed cytokine as well as cellular-based immunologic treatments for cancer. During the next several years, physicians and scientists alike will need to critically appraise the results of clinical trials of some of these novel treatment approaches and determine how they will fit in with the existing options for the treatment of patients with head and neck cancer. Given that these tumors arise from multiple molecular aberrations, it is likely that biological therapies will be used in combination with other biological approaches or more conventional treatment modalities.