Contemporary concepts of open angle glaucoma suggest that the current emphasis on reduction of elevated intraocular pressure could be augmented by other therapeutic approaches. In this article, we describe significant recent developments in the molecular and cellular biology and neuropharmacology of nerve damage that are likely, in coming years, to suggest new therapeutic approaches to the management of glaucoma. These developments may lead to the achievement of pharmacologic protection of the optic nerve from damage or possibly promotion of reversal of damage. We review selected studies of excitotoxins and N-methyl-D-aspartate receptor antagonists, Ca2+-induced damage and calcium channel blockers, the intracellular messenger nitric oxide and its perturbation, free-radical damage and scavengers, nerve regeneration, and growth factors. Several basic research questions are posed, answers to which may transform our concepts of glaucoma therapy.