Immunotherapy remains a hot topic with an endless stream of new upcoming clinical trials. The results of studies to date are promising for second-line palliative treatment of head and neck squamous cell carcinoma (HNSCC). The next step is testing these strategies in randomized trials for first-line and curative treatment in an adjuvant, neoadjuvant, and primarily nonsurgical setting. So far, established biomarkers have not proven reliable enough to predict response rates precisely.On occasion of the annual meeting of the American Society of Clinical Oncology (ASCO), we aimed to invesitage the future of immunotherapies.We collected the most promising upcoming studies alongside current research in the field of biomarkers with a view to interesting new immunotherapeutic strategies.The search for appropriate biomarkers in particular seems to be a central research objective in the short term. There is a broad range of new agents that will be tested in clinical trials as well as the combination of immunotherapy with chemo- and chemoradiotherapy or other immune-modulating drugs.The real challenge will be to find the most fitting therapy for each patient out of a large panel of available regimens. Therefore, it is most important to find a set of reliable biomarkers that together could predict treatment response.