The optic nerve, or the second cranial nerve, is the most important structure in the eye to maintain vision. Diseases affecting the optic nerve can cause subtle visual loss and visual field defects, which in the advanced stages can lead to complete blindness. In the eye, the optic nerve head can be visualized and can be an indicator of both ocular as well as central nervous system disease. This nerve can be afflicted by inflammation, ischemia, and compressed by tumors. Several congenital anomalies are also known. Each of these unique disorders may be associated with varying systemic associations, which, when detected early in the course, can not only preserve vision but also, as in the case of CNS or vascular involvement, is life-saving. This chapter discusses the various disorders affecting the optic nerve.