The first mention of retinoblastoma (RB) as an ocular tumor likely date back to the 17th century when it was described that there exist a malignancy invading the orbit, temporal region and cranium, which fits the description of untreated RB. RB occurs in heritable or nonheritable forms that are associated with the presence or absence of germline RB1 gene mutations, respectively. Hereditary RB is usually characterized by bilateral or multifocal unilateral eye tumors, a positive family history of RB (in ~10% of cases), a younger median age at diagnosis, an increased risk to develop trilateral RB as well as second malignant neoplasms, and a 50% risk to transmit the trait to develop RB to future offspring. Nonhereditary RB is typified by the presence of unilateral eye tumors, but no increased risk of second malignant neoplasms or to transmit the trait to future offspring. Clinical genetic testing improves patient outcome by enabling appropriate primary tumor treatment as well as surveillance for additional eye and other tumors.