Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) developed from the amino-acid composition of epithalamin, a pineal-derived polypeptide preparation. Although historically related, the two preparations are chemically distinct and their evidence should not be considered interchangeable. This narrative review examines the mechanistic, preclinical, and human evidence for epitalon, with epithalamin studies considered separately as historical context. The strongest mechanistic evidence for epitalon involves telomerase activation and telomere elongation in human cell lines. These findings were independently replicated in 2025, with telomere extension occurring through hTERT/telomerase upregulation in normal cells and alternative lengthening of telomeres in cancer cell lines.[1] Preclinical studies have also reported age-dependent neuroendocrine effects, antioxidant-associated activity, and tissue-protective effects. In female mice, epitalon did not increase mean lifespan but increased maximum lifespan by 12.3%.[2] Human epitalon evidence remains limited to small physiological or biomarker studies and an older report in retinitis pigmentosa; no adequately powered randomized trial has established therapeutic efficacy.[1,3,4] Historical epithalamin studies have reported neuroendocrine, antioxidant, cardiovascular, and longevity-associated outcomes, but these findings cannot be directly extrapolated to epitalon. Human pharmacokinetic, dose-ranging, and dedicated prospective safety studies remain unavailable, while telomere-maintenance effects raise theoretical but unresolved questions regarding long-term oncologic safety. FDA reviewed epitalon free base and acetate through the 2026 PCAC compounding process, which does not constitute therapeutic approval. [5] Overall, epitalon demonstrates biologically relevant activity but remains clinically unproven. Independent replication, pharmaceutical characterization, pharmacokinetic and safety studies, disease-specific preclinical models, and appropriately designed human trials are needed before its role in regenerative or longevity medicine can be established.