It might seem odd that a special issue about Gianni Bonadonna would publish a review on radiation-induced neurocognitive dysfunction. Dr. Gianni Bonadonna is considered a pioneer in medical oncology history, mainly due to new and revolutionary treatment approaches proposed in breast cancer and Hodgkin lymphoma. He had an active role in the field of medical oncology, especially through lectures and textbooks. He shared his considerable insight of understanding cancer behavior and evaluating research advances over the years to prevent tumor recurrence and preserve patients from unnecessary toxicity. From a theoretical point of view, this complex vision is valid for all malignancies and can be indirectly shifted to every primary cancer, including head and neck cancer (HNC). During the last decades, multidisciplinary treatment for HNC has improved clinical outcomes but makes acute and late toxicity challenging. This article highlights the main central nervous structures that have a major impact on the development of neurocognitive dysfunction after radiotherapy for HNC. We briefly summarize the specific structure contouring instructions and the dose-volume histogram parameters. The aim is to raise awareness in clinicians in defining normal tissues to optimize radiotherapy regimens.