Purpose <p>To provide a comprehensive overview of the structural and functional characteristics of the blood-retinal barrier (BRB), examine its critical role in the pathogenesis of major ocular diseases, and summarize current and emerging therapeutic strategies aimed at restoring BRB integrity.</p> Methods <p>A literature search was conducted in PubMed, Scopus, and Web of Science databases, focusing primarily on publications from the past 10 years supplemented by seminal earlier works. This narrative review synthesizes evidence on BRB molecular anatomy, pathological mechanisms, disease-specific roles, and therapeutic interventions.</p> Results <p>The BRB comprises inner (iBRB) and outer (oBRB) compartments with distinct cellular and molecular architectures. BRB dysfunction is driven by convergent mechanisms including aging, hyperglycemia, oxidative stress, inflammation, and hypoxia, which disrupt tight junction proteins and promote aberrant angiogenesis. This barrier breakdown constitutes a pivotal pathogenic driver in major blinding diseases: age-related macular degeneration, diabetic retinopathy and retinal vein occlusion, glaucoma, and uveitis. Current standard treatments include anti-VEGF agents and corticosteroids. Emerging strategies target Wnt/β-catenin signaling, employ senolytic therapies, utilize biomaterial-based drug delivery, and develop organ-on-a-chip models for personalized medicine.</p> Conclusions <p>BRB disruption represents a critical inflection point in ocular disease progression, triggering self-perpetuating cycles of neuroinflammation and degeneration. Effective restoration requires multi-faceted approaches combining anti-angiogenic, antiinflammatory, and barrier-strengthening mechanisms. Future research should focus on dynamic functional assessment, single-cell multi-omics integration, and adaptive therapeutic strategies to prevent irreversible vision loss.</p>