Glaucoma is unique among ophthalmic diseases since its underlying pathophysiology involves structures in both the anterior and posterior segments of the eye. Concepts relating to glaucoma have evolved as our understanding of the disease processes has increased. Glaucomatous optic neuropathy is the end result of several cellular disease phenomena. Glaucoma results in loss of neuronal and axonal architecture, activation of glial cells, tissue remodeling and changes in ocular blood flow, but the order in which pathological changes occur has yet to be determined. Although elevated intraocular pressure is the primary risk factor for disease development, it has been excluded from the definition of glaucoma that can exist, or even progress, despite ‘normal’ or significantly reduced levels of intraocular pressure. The aim of this chapter is to summarize the basic mechanisms that underlie the impairment of aqueous outflow in glaucomatous eyes and describe various pathogenic pathways that contribute to the death of retinal ganglion cells, the common end point of all types of glaucoma.