Glaucoma results from the degeneration of retinal ganglion cells and their axons. Over the last 20 years several important advancements have been made in our understanding of the molecular pathology of this disease, particularly through the development of rat models of experimental glaucoma and the characterization of a spontaneous secondary form of glaucoma in DBA/2 substrains of inbred mice. One of these advances is the observation that ganglion cells die by apoptosis, an intrinsic molecular pathway of programmed cell death. An important aspect of this cell death process is the concept that these cells actually undergo compartmentalized self-destruction. Importantly, genetic evidence now suggests that axons die independently of the apoptotic program that executes the cell body or soma. This review briefly summarizes some of the most significant developments in glaucoma research, with respect to the process of ganglion cell degeneration.