Neuronal tissues such as the retina contain high amounts of plasmalogens. One of their particularities is to concentrate polyunsaturated fatty acids (PUFA) before releasing them specifically. Several data from our laboratory suggest that plasmalogens are involved in the pathophysiology of primary open angle glaucoma (POAG), the second leading cause of blindness worldwide. The different experiments were carried out on human patients with POAG as well as on rodent models of glaucoma. They concerned either the identification of specific alterations of plasmalogen metabolism, or the efficacy of PUFAs to prevent retinal damage. The results have shown a loss of several circulating plasmalogens in human POAG patients. This was stage-dependent and may have started years prior to first clinical diagnosis. In animals, several combinations of PUFAs were efficient in preventing/treating retinal glaucomatous damage. The biophysical and biochemical properties of plasmalogens are very consistent with a protective role in the pathogenesis of POAG.