The prognosis of patients with advanced head and neck cancer has not changed significantly in the last twenty years, despite concerted efforts to optimize treatment using conventional modalities such as surgery, radiotherapy and chemotherapy. Novel therapeutic approaches based on our increasing understanding of the molecular changes that underlie the development of cancer have the potential to alter this situation. Gene therapy involves the delivery of genetic sequences in to tumour or normal cells for a therapeutic purpose. A number of viral and non-viral vectors have been developed that have the ability to deliver therapeutic genes specifically to tumours. These therapeutic genes can exert their effects by correcting existing genetic abnormalities, by killing cells directly or indirectly through recruitment of the immune system. In this review, the various gene therapy strategies that are under development are presented with particular reference to the treatment of head and neck cancer.