Increased intraocular pressure is the strongest correlated modifiable risk factor for developing primary open-angle glaucoma (POAG). Lipids have long been known to be a major constituent of aqueous humor. Lipid mediators, prostaglandins for example, are the first-line treatment for glaucoma. Innovative technologies have made the investigation of lipids in small quantities possible, and interest in identifying lipids as new pharmacological targets has grown in ophthalmology. There is expanding evidence to suggest that lipids and their active metabolites play a role in POAG pathophysiology, as differences between control and diseased eyes have now been demonstrated. The role of these differences is yet to be determined and is the subject of this review.