Head and neck cancers (HNC) include malignant tumors that grow in and around the mouth, larynx, throat, sinuses, nose, and salivary glands. Accumulating evidence in malignancies suggests the aberrant expressions of the estrogen receptor (ER) and the androgen receptor (AR) in HNC, such as in laryngeal cancer and cancer of the salivary gland. Moreover, the signaling pathways involving these receptors that mediate tumorigenesis, proliferation, apoptosis, migration, and invasion have been elucidated. This review summarizes the roles of ER and AR with the putative signaling pathways involved in HNC. We also discuss the potential application of ER-and AR-related therapies in HNC. However, most of the mechanisms underlying AR and ER involvement in the development of HNC remain elusive and warrant further studies. A comprehensive understanding of the functional roles and mechanisms of action of AR and ER in HNC will facilitate the development of better therapeutic strategies for this disease. Overall, studies on AR and ER provide a promising potential for the diagnosis and treatment of HNC in the future.