Oral/head and neck cancer is the sixth most common human malignancies in the world. Despite the treatment advances in surgery, chemotherapy, and radiotherapy, the patient survival has not been significantly improved in the past several decades. As a new methodological approach, metabolomics may help reveal the metabolic reprogramming mechanisms underlying head and neck cancer cell proliferation, invasion, and metastasis and may be used to identify metabolite biomarkers for clinical applications of the disease. In this chapter, we briefly review recent metabolomic applications in head and neck cancer.