<p>Copeptin, an inert peptide derived from provasopressin and co-released with arginine vasopressin (AVP), has emerged as a stable circulating indicator of AVP system activation and has attracted growing interest in acute ischemic stroke (AIS). Over the past decade, both experimental and clinical investigations have explored its potential clinical relevance. A central challenge, however, is to distinguish the biological role of AVP signaling from the interpretive significance of copeptin as a biomarker. Current evidence indicates that AVP signaling may contribute to key pathological processes, including cerebral edema formation and post-ischemic inflammatory responses. In contrast, copeptin appears to reflect activation of the neuroendocrine stress axis rather than acting as a direct effector within these pathways. Clinically, copeptin levels rise rapidly during the early phase of AIS and are consistently associated with stroke severity and adverse outcomes, supporting its potential utility in early risk stratification and prognostic assessment. The use of copeptin in combination with neuroimaging parameters and other biomarkers has been explored, with some studies suggesting improved performance in early clinical evaluation. However, whether copeptin confers meaningful incremental value beyond established tools remains uncertain. Interpretation of the available evidence is further limited by heterogeneity in study design, variability in sampling strategies, the lack of standardized cutoff values, and the scarcity of large-scale prospective validation. Taken together, copeptin may serve as a useful component within multimarker frameworks for AIS. Its clinical interpretation, however, should remain anchored to its role as a surrogate indicator of AVP pathway activation, rather than being extended to a direct mediator of ischemic injury.</p>