The detection of metastases in patients with a diagnosis of uveal melanoma (UM) is a controversial issue. While only 1% of the patients have detectable metastases at the time of diagnosis, up to 30% of them will develop liver metastases within 5 years of treatment. UM spreads hematogenously, therefore, blood biomarkers may be helpful for prognosis and monitoring the disease progression. Despite the great progress achieved thanks to the genetic analysis of UM biopsies, this is an invasive technique and is limited by the heterogeneity of the tumor. The present review considers the current understanding in the field regarding biomarkers for the diagnosis and prognosis of UM and its metastasis, primarily to the liver. General covered topics include non-conventional markers such as proteins previously identified in cutaneous melanoma and UM cell lines, circulating tumor cells, microRNAs (miRNA), and circulating DNA, and how each may be critical in the development of novel blood biomarkers for UM.