Precision medicine is nothing new in health context, neither in oncology clinical practice. Although, focusing on the "individual" remains trendy, actual, relevant and opportune either for clinical practice, research purposes and particularly, for patients' lives. Patient-reported outcomes are multidimensional and subjective measures that can be objectively quantified. They reflect patients' perceptions about their healthstatus, symptoms, functioning, satisfaction degree with healthcare, health behaviors and health related quality of life. Patient-reported outcomes can capture the voice and experience during the head and neck patient disease journey favoring communication and shared decision-making and engaging both patients and healthcare providers. This approach can demystify procedures, clarify concerns about future and favors emotional support. Moving towards personalized healthcare in head and neck cancer clinical practice brings us emerging challenges in the next few years. Pharmacogenomics, gene testing, health outcomes measures, and patient-reported outcomes are all crucial tools to find a direction and achieve the common objective: find the best path forward! The patient is the keystone!