The “Reference Case” was developed to facilitate comparability among published cost-effectiveness analyses intended to contribute to decisions about the broad allocation of healthcare resources. Although the societal perspective is recommended for Reference Case analyses, empirical estimations rarely adequately represent the patient perspective, and more often, healthcare system or payer perspectives are used. In this commentary, we discuss the evolution of the Reference Case over the past 20 years and how it now needs to further evolve. This should begin with a patient-informed societal perspective. A realignment of the societal perspective to better include patient perspectives in CEA creates a conduit for patient inclusion. Engaging patients to both derive patient-informed value elements and prioritize value elements using stated preference methods will lead to patient inclusion in the societal perspective and a patient-informed Reference Case analysis.