In the era of precision oncology, major strides are being made to use individual tumor information for clinical decision-making. Differing from traditional biopsy methods, the emerging practice of liquid biopsy provides a minimally invasive way of obtaining tumor cells and derived molecules. Liquid biopsy provides a means to detect and monitor disease progression, recurrence, and treatment response in a noninvasive way, and to potentially complement classical biopsy. Uveal melanoma (UM) is a unique malignancy, with diagnosis heavily reliant on imaging, few repeat biopsies, and a high rate of metastasis, which occurs hematogenously and often many years after diagnosis. In this disease setting, a noninvasive biomarker to detect, monitor, and study the disease in real time could lead to better disease understanding and patient care. While advances have been made in the detection of tumor-disseminated components, sensitivity and specificity remain important challenges. Ambiguity remains in how to interpret current findings and in how liquid biopsy can have a place in clinical practice. Related publications in UM are few compared to other cancers, but with further studies we may be able to uncover more about the biology of disseminated molecules and the mechanisms involved in the progression to metastasis.