Radiation therapy for cancer often results in xerostomia, also known as dry mouth, which significantly impacts oral health and can lead to tooth loss. Saliva is crucial in maintaining dental health by preventing cavities, gum diseases, and tooth erosion. However, reduced saliva production due to radiation therapy can disturb this delicate balance and make teeth more prone to various problems. Xerostomia can further exacerbate these problems and hinder oral tissue healing and regeneration abilities, leading to severe consequences like tooth loss. Proactive management techniques are crucial in reducing the impact of xerostomia on tooth loss. These techniques include using saliva substitutes, regular dental check-ups, and strict oral hygiene practices. However, it is essential to comprehend the processes behind this phenomenon to understand the pathophysiology of dry mouth and create specific therapies to reduce its effects. If well understood, healthcare providers and radiation oncologists can provide appropriate preventive measures and improve the oral health of patients with head and neck cancer undergoing radiation therapy by understanding and managing the complexity of this interaction. Hence, this chapter briefly overviews the possible and established connections between xerostomia and tooth loss and the underlying mechanisms.