There is a long-standing convention to irradiate the great majority of head and neck squamous cell carcinoma (HNSCC) electively to both sides of the neck, to reduce the theoretically increased risk of contralateral regional failure (cRF). With the currently available diagnostic imaging techniques this treatment paradigm means, in our opinion, an overtreatment in considerable proportion of these patients. From all the published studies (n = 11, with 1116 patients treated in total), the incidence of cRF in patients with oropharyngeal cancer treated to one side of the neck is 2.4%. The incidence was higher in patients with tumours involving the midline (12.1%). The low incidence of cRF was also seen in patients with HNSCC treated by local excision combined with unilateral neck dissection or sentinel node procedure. It seems clear from the aggregated data of these studies that a less conservative approach with regard to the selection of patients for unilateral elective nodal irradiation is justified. The fear of leaving the contralateral neck untreated in well-selected groups of patients with HNSCC needs nowadays to be mitigated since the incidence of cRF in lateralised tumours extending to but not crossing the midline is low. Furthermore, the obviously improved diagnostic imaging nowadays could help us to guide the selection of considerable proportion of patients with lateralised HNSCC for unilateral elective nodal irradiation with significant reduction of radiation-related toxicity and improved quality of life.