Over the past decades, the survival rate of head and neck cancers has not significantly changed. Recently, the importance of the inflammatory responses in head and neck cancer has been a hot topic and of increasing interest. There has been suspicion about the relationship between inflammation and carcinogenesis, and thus, many works had proven these relations. Manipulation of the inflammatory mediators has been experimented with, to reduce the tumor burden, treat as well as prevent the cancer occurrence or second primary. This chapter summarizes the relationship between inflammation and cancer, emphasizing epidemiological and clinical evidence and proposing the current potential targets of anti-inflammatory agents for the therapeutic approach of head and neck cancer (HNC). We hope this knowledge will help us combat carcinogenesis and reduce the morbidity of the current conventional treatment for a better quality of life.