The 2024 revisions of the McDonald diagnostic criteria include the optic nerve as a fifth anatomical location within the CNS for the diagnosis of multiple sclerosis, in addition to periventricular, juxtacortical or cortical, infratentorial, and spinal cord lesions. Demonstration of dissemination in space can now be achieved with the detection of typical lesions in at least two of these five locations. We review the evidence supporting the use of optical coherence tomography (OCT) and visual evoked potentials (VEPs) to show optic nerve involvement in the diagnosis of multiple sclerosis. We also report consensus recommendations for their use. Provided there is no better explanation for optic nerve involvement and that rigorous quality control is applied, OCT-derived peripapillary retinal nerve fibre layer inter-eye differences of 6 μm or greater or composite macular ganglion cell and inner plexiform layer inter-eye differences of 4 μm or greater support optic nerve injury. Delayed VEP latency, which depends on technical and methodological factors, and is centre and device dependent, supports demyelinating optic nerve injury when done with appropriate technical knowledge and interpretation.