Recent data have provided important clues about the molecular mechanisms underlying certain retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration. Photoreceptor cell degeneration is a feature common to these diseases, and the death of these cells in many instances seems to involve the closely associated retinal pigment epithelial (RPE) cells. Under normal circumstances, both cell types are subject to potentially damaging stimuli (e.g. sunlight and high oxygen tension). However, the mechanism or mechanisms by which homeostasis is maintained in this part of the eye, which is crucial for sight, are an unsolved riddle. The omega-3 fatty acid family member docosahexaenoic acid (DHA), which is enriched in these cells, is the precursor of neuroprotectin D1 (NPD1). NPD1 inhibits oxidative-stress-mediated proinflammatory gene induction and apoptosis, and consequently promotes RPE cell survival. This enhanced understanding of the molecular basis of endogenous anti-inflammatory and neuroprotective signaling in the RPE presents an opportunity for the development of therapies for retinal degenerative diseases.