Glaucoma is a group of multifactorial, neurodegenerative diseases characterized by slow progressive damage to the optic nerve and retinal ganglion cells (RGCs). Visual field defects corresponding to the damage can be identified. Traditionally, elevated intraocular pressure (IOP) is regarded as the most important risk factor and the possible primary insult in glaucoma. However, lowering the IOP is unable in some cases to control progressive optic nerve damage and prevent further vision loss satisfactorily. Hence, additional treatment strategies are needed. Currently, the focus of research in glaucoma treatment is shifting toward neuroprotection, which may be defined as the protection of undamaged RGCs and the rescue of injured RGCs by therapeutic agents or through molecular and cell-based approaches. In this article, three mechanisms of glaucoma neurodegeneration (the mechanical theory, the vascular hypothesis and autoimmunity) will be discussed, and possible targets for glaucoma neuroprotection will be identified. In addition, we will evaluate currently advocated neuroprotective drugs and discuss their potential in the management of glaucoma. Finally, we will also review novel molecular and cell-based approaches as well as a variety of experimental strategies for neuroprotection against glaucoma. There is, indeed, a wealth of knowledge may help to identify effective glaucoma neuroprotection. The challenge now is how to assess the way forward to make this approach become useful.