The pathogenesis of the diseases termed open-angle glaucoma remains elusive but progress is being made in understanding more clearly the optic nerve head, vascular, and cellular mechanisms that are associated with them. Even though the greatest risk factors remain intraocular pressure, age, race and refractive error, the association with vascular disease continues to unfold in the literature. Clinical and laboratory studies, although not addressing mechanisms directly as far as we know, continue to probe potential pathways that will ultimately lead to subsets of open-angle glaucoma. Only when this is accomplished will we be able to focus therapy at pathogenesis rather than at risks.