Uveal melanoma is the most common neoplasm of the adult eye. Many patients will develop metastatic disease, for which there is no standard of care. Therefore, we sought to review our experience with treating this neoplasm. We retrospectively reviewed all of the cases of metastatic uveal melanoma seen at the Mayo Clinic, Rochester, Minnesota, USA, between 1 January 2000 and 1 August 2013. Overall survival rates were compared among patients treated with local therapies (LTs), ipilumumab, bevacizumab, or kinase inhibitors. A total of 101 patients were included in the study, among whom 59% were male; the median age was 62 years (interquartile range 54-71), and 92% had an Eastern Cooperative Oncology Group performance status of 0-1. Treatment with LT was associated with increased median overall survival: 26 months (n=46; interquartile range 20-44) versus 9.1 months (n=55; 4.1-20, P<0.0001). No significant survival benefit was seen with the use of bevacizumab (25 vs. 12 months; P=0.09), ipilimumab (28 vs. 13 months; P=0.07), or kinase inhibitors (24 vs. 13 months; P=0.06). Multivariate analysis showed LT as the only therapy to significantly improve survival (risk ratio 0.23, P=0.0003). However, these patients had better markers of prognosis at the time of treatment. These data suggest that survival was improved in patients who were amenable to LTs; however, they had better prognostic markers at diagnosis of metastatic disease. Ongoing prospective clinical trials will define the roles of these novel agents in this patient population.