The optic nerve, also known as the second cranial nerve, is composed of axons that transmit visual information from the neurosensory retina to the visual cortex. There are multiple pathologies that can affect the human optic nerve. Congenital anomalies of the optic nerve include myelinated nerve fibers, morning glory syndrome, optic nerve choristoma, optic nerve coloboma, optic nerve hypoplasia and aplasia, and others. Tumors that can affect the optic nerve (ON) may occur primarily from within the nerve itself, from the surrounding optic nerve sheath (ONS), or secondarily spreading to the nerve from a distant site. They include optic pathway glioma, medulloepithelioma, oligodendroglioma, optic nerve sheath meningioma, and others. Here in this chapter, we will review the optic nerve anatomy, embryology, and physiology in addition to assessment of optic nerve function. Moreover, the clinical features, imaging findings, pathology, and treatment options of the most common and some rare congenital anomalies and primary tumors of the ON and sheath will be reviewed.