Uveal melanoma has traditionally been treated with enucleation, plaque brachytherapy, or external beam radiation. Following the results of the multicenter Collaborative Ocular Melanoma Study (COMS), which established no significant difference in mortality rates between enucleation and brachytherapy, plaque brachytherapy has become the favoured modality given its potential for preservation of vision and the eye. Among the radioisotopes that have been used, iodine-125 (I-125) has become the increasingly popular choice in the United States. However, I-125 brachytherapy is associated with complications, including keratitis, iris neovascularization, neovascular glaucoma, radiation retinopathy, and optic neuropathy. The purpose of this review is to discuss the pathogenesis, clinical presentation, and management of complications related to I-125 plaque brachytherapy for choroidal melanoma.