.....Over the past decade, the primary human fetal RPE (hfRPE) culture model has emerged as an effective tool for studying RPE function and mechanisms of retinal diseases. This model system has been rigorously characterized and shown to closely resemble native RPE cells at the genomic and protein level, and that they are capable of accomplishing the characteristic functions of a healthy native RPE (e.g., rod phagocytosis, ion and fluid transport, and retinoid cycle). In this review, we demonstrated that the metabolic activity of the RPE is an indicator of its health and state of differentiation, and present the hfRPE culture model as a valuable in vitro system for evaluating RPE metabolism in the context of RPE differentiation and retinal disease.