Glaucoma is the second leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is characterized by optic disc cupping and visual field impairment. Though the elevated intraocular pressure (IOP) is thought to be the major risk factor for POAG, about 50% of the POAG patients have normal IOP, called 'normal-tension' glaucoma. Besides, many POAG patients still experience visual field loss and/or optic disc cupping even though the IOP has been well controlled. The mechanisms underlying the pathogenesis of POAG remain unclear. Extensive studies have shed lights on the mechanisms that may be involved in the etiopathology and/or the optic neuropathic manifestations of POAG. In this article, we noticed that the changes in the cerebrospinal fluid, particularly that existing in the subarachnoid space of the optic nerve, appear to be actively involved in the pathogenesis of POAG.