Although overall cancer death rates are decreasing, comparative improvements in head and neck squamous cell cancer are modest. Although new advances targeting immune checkpoints may soon improve these numbers, additional research for new therapeutic options is vital. One potential treatment avenue is the use of gene therapy. This article provides insight into some gene therapy targets and varied techniques being evaluated for patients with head and neck cancer. Techniques include corrective gene therapy, cytoreductive gene therapy, and gene editing, in addition to a discussion on gene therapy vectors.