Several new chemotherapy agents show varying degrees of activity in head and neck cancer. The most extensively studied and most promising agents at this time are the taxanes, particularly paclitaxel. Its exact role in combination with other chemotherapeutic agents or with radiation is still being clarified in clinical testing, but it is certainly reasonable to use paclitaxel for palliation of metastatic or recurrent disease. Docetaxel is a more recently developed agent, and more information regarding its use in palliative therapy will be forthcoming as results from the international randomized trial become available. Gemcitabine has shown very modest activity when used as a single agent or in combination therapy, although further data from ongoing research have not yet been reported. It is an extraordinarily potent radiosensitizer in the head and neck, but unfortunately it appears to have a very narrow therapeutic ratio and should certainly not be used with radiation outside of a clinical trial with careful monitoring of toxicity. Topotecan does not appear to be a clinically useful single agent in treating head and neck cancer, and vinorelbine has shown minimal activity in the few clinical trials that have been conducted in head and neck cancer. Nedaplatin is a very new drug, and it is not possible to draw conclusions regarding its effectiveness until further evaluation has been completed. Continued investigation of new chemotherapeutic agents in head and neck cancer is needed.