Many patients with uveal melanoma die as a result of metastatic spread despite successful treatment of the primary tumor. This raises important and unsettling questions about how and in whom ocular treatment influences survival, if at all. Such questions cannot be fully answered without a proper understanding of the natural history of uveal melanomas, particularly in relation to the time of onset of metastatic spread. The lack of firm evidence on which to base patient care complicates decision-making regarding matters such as the treatment of small melanocytic tumors of indeterminate malignancy and screening for metastatic disease.