OBJECTIVES: To review the epidemiology, prognostic factors, and treatment guidelines for recurrent or metastatic HNSCC, to better understand and describe patient groups and the corresponding treatment options. METHODS:  Targeted literature reviews of published epidemiology studies in the past five years and current clinical guidelines from Europe, North America, and Australia indexed in the National Guideline Clearinghouse or International Guideline Library were conducted. RESULTS: Of 265 hits, 25 epidemiology studies and 12 guidelines were selected. Global incidence and one-year prevalence rates in 2012 were 1.9 and 1.7 per 100,000 (oropharynx/hypopharynx), 2.1 and 2.2 (larynx), and 4.0 and 3.9 (lip/oral cavity), respectively. Changes in annual incidence rates (-3.7% to +5%) vary by tumor site, gender, and country. Risk factors for advanced HNSCC include age, gender, and alcohol or tobacco use, whereas risk factors for recurrence or death include tumor characteristics and treatment outcome. Five-year survival rates for metastatic HNSCC ranged widely between 3–36% across tumor sites and studies. In Europe and the United States, depending on tumor site, 2–16% of HNSCC are diagnosed at distant stages. Reportedly, 35% of regional cases develop distant metastases, including 25% of complete responders. Epidemiological data on recurrent vs. metastatic disease, or relapse vs. refractoriness to prior therapies is scarce, fragmented by tumor site/subsite, and limited to single study sites/countries. Newer guidelines recommend combined platinum/5-fluorouracil FU/cetuximab for recurrent/metastatic HNSCC. However, no recommendations are based on prior systemic therapy, nor differentiate recurrent and refractory disease. CONCLUSIONS:  Epidemiological data on HNSCC sub-populations not amenable to curative treatment is scarce and fragmented by country and disease site, resulting in low generalizability. A more comprehensive systematic review or chart reviews may provide further informative epidemiological data. However, we can conclude that in non-curative disease, there remains high unmet need with limited systemic treatment options available and poor overall survival.