Background: Intravitreal vascular endothelial growth factor (VEGF) inhibitors represent the mainstay of neovascular age-related macular degeneration (nAMD) treatment. Although bevacizumab has been the first anti-VEGF used in ophthalmology, it is unlicensed for intraocular use. However, the favourable cost-benefit balance has favoured its widespread use. We aimed to present relevant literature regarding the safety profile and the regulatory issues of intravitreal bevacizumab use. Methods: In this narrative review we report relevant studies regarding the safety profile of intravitreal bevacizumab. Expert commentary is provided and an overview of the current scenario and possible future directions discussed. Results: Randomized controlled trials have demonstrated that bevacizumab is not inferior to the licensed anti-VEGF agents showing similar efficacy and safety profiles. However, a significant debate on the regulatory issues of intravitreal bevacizumab used as ‘off label’ first-line treatment in nAMD still persists. Recently, the Regional Health System of Lombardia in Italy decided to only cover the expenses of bevacizumab, forcing clinicians to use bevacizumab as the first choice in the treatment of nAMD. Issues about the practical implications of this decision are discussed. Conclusion: The use of intravitreal bevacizumab as first-line therapy in nAMD remains controversial. Many differences in the regulatory aspects still persist among the European countries and sometimes within the same countries, like Italy. Of note the clinical scenario will be modified in future by the introduction of newly developed anti-VEGF agents and anti-VEGF biosimilars.