Uveal melanoma is a rare, aggressive cancer arising from melanocytes of the uveal tract. It is the most common primary intraocular malignancy in adults. Despite excellent rates of local disease control, nearly 50% of patients will develop metastatic disease, with the most common initial site being the liver. Outcomes are poor following the development of distant disease, with a median survival of under 24 months. Advances in molecular profiling have enabled a more accurate prediction of metastatic risk. Given the poor prognosis associated with metastatic disease, the development of effective adjuvant therapies that prevent the development of recurrence is critical to the management of high-risk patients. In this chapter, we provide a comprehensive review of the historical, current, and future approaches to adjuvant therapy, including chemotherapy, targeted therapy, immunotherapy, epigenetic drugs, liver-directed therapy, and other novel treatment strategies.