Renewal and elimination of aged photoreceptor outer segment (POS) tips by cells from the retinal pigment epithelial (RPE) is a daily rhythmic process that is crucial for long-term vision. Anomalies can arise during any of the sequential steps required for completion of this phagocytic function, from POS recognition to complete digestion of POS components. During the past 15 years, many animal models helped us characterize the molecular machinery implicated in RPE phagocytosis as well as understand associated defects leading to various retinal pathologies. Depending on which part of the machinery is flawed, phenotypes can either appear early in life, such as retinitis pigmentosa or Usher syndrome, or develop with aging of the individual, like age-related macular degeneration, affecting first either the peripheral or the central retina. This chapter describes mouse and rat models related to defective phagocytosis, and how they have been a tremendous help for us to comprehend RPE phagocytosis, its rhythm, and its failures.