This article discusses mimics of multiple sclerosis (MS). Excluded in this discussion are neuromyelitis optica and vasculitis, discussed in other articles in this journal. Covered entities include posterior reversible encephalopathy syndrome, reversible vasoconstriction syndrome, acute disseminated encephalomyelitis, Sussac's Syndrome, and chronic idiopathic demyelinating polyneuropathy. There are also multiple infectious entities that mimic MS including; progressive multi-focal leukoencephalopathy (PML), Toxoplasmosis, Tuberculosis, Herpes Simplex Virus, Cytomegalovirus, Varicella zoster virus, Epstein Barr virus, Cryptococcus and Human immunodeficiency virus. In addition, there are leukoencephalopathies that can present in adulthood including Adrenoleukodystrophy, Metachromatic leukodystrophy, Cerebral autosomal dominant idiopathic leukoencephalopathy, Leigh's and Alexanders disease that could be mistaken for MS.