Brachytherapy with an iodine-125 or ruthenium-106 plaque is the first choice of treatment for uveal melanomas in most centers. Local tumor control and prevention of avoidable ocular morbidity require meticulous preoperative assessment, expert radiation dosimetry, safe treatment planning, good surgical technique, long-term surveillance, and proper treatment of any side effects and complications. The most serious complication is local tumor relapse, which appears to be associated with increased metastatic mortality. It is useful to distinguish between collateral damage to healthy ocular tissues when these receive high-enough levels of radiation, and toxic tumor syndrome, caused by intra-tumoral radiation-induced vasculopathy, with exudation, retinal detachment, production of angiogenic factors, iris neovascularization, and neovascular glaucoma.