Introduction: Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Almost 2/3rds of patients have recurrent or metastatic (R/M) HNSCC. Treatment options for R/M HNSCC have evolved, with relatively little change in survival. Thus, it is imperative that management decisions must balance efficacy with toxicity and emphasize the importance of maintaining the patient's quality of life (QOL). Areas covered: We cover the various chemotherapeutic options available for R/M HNSCC including single agent chemotherapy, platinum-based doublets and triplet options. The role of cetuximab, immunotherapy and oral metronomic chemotherapy (OMCT) is also reviewed. We discuss the management of patients with platinum-refractory disease. Expert opinion: In all patients with R/M HNSCC, we recommend assessment of extent of disease, patient symptomatology, performance status, affordability and availability of logistic and social support. In patients with PD-L1 CPS =/> 20, pembrolizumab is an option. In patients with PD-L1 CPS < 20, pembrolizumab/cisplatin/5FU or cisplatin/5FU/cetuximab (EXTREME) may be considered based on affordability and availability. Options available that have a lower toxicity and can help to maintain the patient's QOL include; single agent chemotherapy, carboplatin/paclitaxel combination chemotherapy, sequential combination chemotherapy followed by cetuximab, replacing 5FU with docetaxel (TPEx regime) and OMCT.