As the biopharmaceutical industry strives to address areas of high unmet medical need, there is increasing reliance on novel endpoints to accelerate and support drug development. In rare diseases, traditional clinical outcomes may take too long to manifest, delaying access for patients with limited time and small populations. In chronic conditions, conventional endpoints can constrain innovation by overlooking meaningful aspects of disease that matter most to patients. This discussion will explore three critical areas for advancing the use of novel endpoints. First, optimizing sponsor submissions to clearly and persuasively present data supporting innovative endpoints. Second, strengthening FDA–sponsored collaboration to ensure comprehensive evaluation of disease manifestations and patient-relevant outcomes. Third and final, improving FDA transparency in documenting its rationale around endpoint acceptance, to facilitate learning for industry, clinicians, and patients.