Head and neck cancer (HNC) survivors frequently experience depression, which confers worse survival, elevated suicidality, and poor quality of life. The National Comprehensive Cancer Network and other stakeholders recognize this and offer guidance regarding screening, identification, and treatment of depression and anxiety in patients with cancer.¹ However, their stance remains largely reactive rather than proactive, and guidelines do not currently acknowledge prevention strategies for depression. This is a missed opportunity to improve survivorship experiences of patients with HNC. In this Viewpoint, we advocate for prophylactic antidepressant use for depression prevention in patients undergoing treatment for HNC, propose areas for additional research, and urge various guideline-setting organizations to include recommendations for depression prevention in guidelines for comprehensive care for patients with HNC.