For a new intervention to achieve commercial success, regulators (to provide marketing authorisation), payers (for reimbursement and formulary placement), healthcare professionals (HCPs; to prescribe) and patients (to adhere and persist) must all consider the intervention to be valuable. These stakeholders are increasingly using the patient's perspective on a condition and its treatment—measured through patient-reported outcome (PRO) instruments—to define the value of a treatment. However, there is common confusion about the most appropriate way to incorporate the patient's perspective into the clinical development of pharmaceutical interventions in a way that will resonate with these four key stakeholder groups. This article briefly summarises the perspectives of regulators, payers, HCPs and patients regarding PRO endpoints, and examines how a robust, comprehensive and systematic PRO endpoint strategy can be developed to meet the needs of all stakeholders in a single development programme. Such an endpoint strategy may include PRO assessments of first-order signs and symptoms using a disease-specific measure, health-related quality of life using both a disease-specific measure and generic utility measure, and general quality of life. Other PRO endpoints (e.g. preference/satisfaction, ease of use, HCP contact time, absenteeism) may be useful with some stakeholders to provide further differentiation between interventions.