Children with retinoblastoma typically survive their cancer due to advances in early diagnosis and treatment. Despite this success, risk factors persist for metastasis that are thought to be related to patient age, sex, laterality, treatment, genetics, histopathology, and extraocular extension. This review has found that invasion of the uvea, orbit, and optic nerve continue to be the most important predictors of metastatic retinoblastoma. Bilaterality and delays in diagnosis are also important factors. We examine molecular and genetic studies that offer the potential of predicting which tumors are likely to metastasize, which will recur within the eye, and which will undergo senescence. In this review, we describe which clinical evaluations, genetic studies, and histopathologic evaluations of retrieved specimens are currently used widely. This review has been performed to help those caring for patients with retinoblastoma and to aid informed consent.