The retina is the most metabolically active tissue in the body. It harbors high levels of flavins due to their involvement as enzymatic co-factors in energy production. Flavins are delivered to the body via specific transporters, the ablation of which leads to riboflavin transporter deficiency (RTD) and ariboflavinosis in humans. RTD leads to embryonic lethality in mice, and in humans, it has detrimental effects on the nervous system, causing neurologic abnormalities. However, the reports on the effects of RTD on retinal homeostasis are limited despite the fact that the retina maintains high levels of riboflavin and its derivatives. We have identified retbindin (Rtbdn) as a retina-specific riboflavin-binding protein, ablation of which leads to reduced flavin levels associated with retinal degeneration in mice. To focus attention on the role of flavins in retinal homeostasis, herein, we discuss the specific functions of flavins and Rtbdn and their protective roles in maintaining retinal health.