Trigeminal neuralgia is a debilitating pain syndrome in the sensory distribution of the trigeminal nerve. Compression of the cisternal segment of the trigeminal nerve by a vessel, usually an artery, is considered the most common cause of trigeminal neuralgia. A number of additional lesions may affect the trigeminal nerve anywhere along its course from the trigeminal nuclei to the most peripheral branches to cause facial pain. Relevant differential considerations are reviewed starting proximally at the level of the brainstem.