Severe and enduring anorexia nervosa (SE-AN) is well known to clinicians who treat eating disorders, especially in adults, yet an empirically validated definition of SE-AN is lacking. Current approaches to delineating SE-AN rely on expert opinion, and there is little consensus regarding the criteria that distinguish SE-AN from other clinical presentations or the thresholds that define the boundaries of severity and enduringness. Empirical classification techniques and clinical staging frameworks that incorporate biomarkers offer intriguing alternatives to expert consensus in refining the definition of SE-AN. Empirical approaches, such as latent class analysis and taxometric analysis, have contributed to advances in eating disorders classification, including support for distinctions between eating disorder classes. Likewise, clinical staging models are being applied to other psychiatric disorders and offer a framework for incorporating biological indices of illness progression, such as neurocognitive changes, into a definition of SE-AN. Though some of these methods (e.g., biomarkers) are a long way from being realized, the need for an evidence-based approach to classifying SE-AN is clear. Without it, the challenges outlined by Wonderlich et al. (International Journal of Eating Disorders, 2020) will be difficult to resolve, and the burden of SE-AN on patients, their loved ones, and the healthcare system will continue.