Eyes with normal-tension and high-tension glaucoma can have a similar optic nerve head appearance, which differs markedly from the optic disc appearance in vascular optic neuropathies. Factors in addition to intraocular pressure (IOP) may play a role in the pathogenesis of glaucomatous optic neuropathy. Clinical and experimental studies have shown (1) physiologic associations between cerebrospinal fluid pressure (CSFP), systemic arterial blood pressure, IOP, and body mass index; (2) that a low CSFP was associated with the development of glaucomatous optic nerve damage in cats; and (3) that patients with normal-tension glaucoma had significantly lower CSFP and a higher trans-lamina cribrosa pressure difference when compared to normal subjects. Due to anatomic reasons, the orbital CSFP and the optic nerve tissue pressure (and not the atmospheric pressure) form the retro-laminar counter-pressure against the IOP and are thus part of the trans-lamina cribrosa pressure difference and gradient. Assuming that an elevated trans-lamina cribrosa pressure difference and a steeper trans-lamina cribrosa pressure gradient are important for glaucomatous optic nerve damage, a low orbital CSFP would therefore play a role in the pathogenesis of normal-tension glaucoma. Due to the association between CSFP and blood pressure, a low blood pressure would also be indirectly involved.