The expiration of patents for ranibizumab and 2-mg aflibercept has enabled the introduction of several anti–vascular endothelial growth factor (anti-VEGF) biosimilars into ophthalmic practice. Simultaneously, recent changes in the French regulatory framework, particularly those introduced by the 2026 Social Security Financing Act, will expand pharmacist-led substitution of biological medicines as of September 1, 2026. These changes raise important questions for ophthalmologists regarding efficacy, safety, immunogenicity, switching strategies, as well as traceability, liability, and patient information. This review summarizes the scientific principles underlying biosimilar development and regulatory approval, highlighting the analytical, preclinical, and clinical requirements necessary to establish biosimilarity. Current evidence regarding ranibizumab and 2-mg aflibercept biosimilars is reviewed, including pivotal clinical trials, switching studies, and recent meta-analyses, all of which support efficacy, safety, and immunogenicity profiles comparable to those of their reference products over the short and medium term. Nevertheless, several ophthalmology-specific considerations deserve particular attention, including physician-administered intravitreal injections, differences in drug presentation, the long-term management of predominantly elderly patients, and the rarity of intraocular inflammatory events. Furthermore, biosimilars are being introduced into a rapidly evolving therapeutic landscape characterized by the emergence of second-generation anti-VEGF agents designed to reduce treatment burden. Biosimilars therefore represent an important opportunity to enhance the sustainability of healthcare systems. Their integration into routine clinical practice, however, should rely on a gradual, individualized approach supported by robust pharmacovigilance.