Chemotherapy has been used for many years as a palliative approach to advanced squamous cell carcinoma of the head and neck. Regimens employed have slowly evolved during this time, and the combination of cisplatin and 5-fluorouracil is still standard chemotherapy for such a tumour. However, clinical approaches to advanced squamous cell carcinoma of the head and neck are changing dramatically as physicians become increasingly familiar with multidisciplinary treatments. Integrating chemotherapy and radiotherapy, neo-adjuvant or adjuvant treatments and organ preservation are stimulating fields of investigation involving chemotherapy which definitely warrant further investigation.