Positron emission tomography (PET) has emerged as an integral diagnostic tool in the management of head and neck squamous cell carcinoma (HNSCC). This article reviews the usefulness and ongoing dilemmas of fluorine-18 fluorodeoxyglucose (18-F FDG) PET and FDG PET/CT in HNSCC. In addition, it examines the potential role of novel markers and biologic characterization of disease, which in the future may assist in targeted therapeutic strategies.