Treatment of vitreoretinal diseases comprises a range of options that has increased in the past several years, allowing more individuals to benefit from new therapeutic approaches. The use of lasers in the retina, new surgical techniques, and intravitreal drug administration constitute common treatment options. These retinal and vitreal procedures have both benefits and drawbacks. Among the drawbacks is discomfort associated with the procedure, constituting a relevant issue because it can compromise adherence to treatment. We reviewed aspects of pain associated with vitreoretinal procedures and the available options for its control. With regard to vitreoretinal procedures, laser photocoagulation is associated with a higher pain score compared with vitrectomy and intravitreal injection using traditional anesthesia methods, suggesting that laser photocoagulation still needs to be improved with regard to comfort during the procedure. In some cases, a combination of analgesic options may be the best choice for pain-sensitive individuals. Individual differences and the specific condition that is treated should be considered when deciding the best treatment option.