Head and neck cancer (HNC) is the sixth most common malignancy world-wide, however the survival rate has not improved for the past 20 years. In recent years, the cancer stem cell (CSC) hypothesis has gained ground in several malignancies and there is mounting evidence suggesting CSCs mediate tumor resistance to chemotherapy and radiation therapy. However, the CSC theory is also challenged at least in certain types of cancer. Here we review the progress of CSC studies in HNC, which suggest that HNC conforms to the CSC model. The identified CSC markers and their tumor initiation properties provide a framework for the development of novel therapeutic strategies for HNC.