Subacute sclerosing panencephalitis (SSPE) is a rare childhood disorder caused by persistent measles virus (MV) infection of the brain that slowly evolves into chronic demyelination and neurodegeneration. Mutant MVs able to spread from cell-to-cell while evading cell-mediated immunity in the brain lead to SSPE 6-8 years after the primary infection. Patients present with behavioral changes followed by progressive myoclonus, seizures, cognitive decline, altered consciousness and death within 1-3 years. Ancillary diagnostic findings include periodic complexes on electroencephalography and intrathecal anti-MV antibodies. SSPE remains fatal despite therapeutic trials. Yet, blockage of MV fusion mechanisms is a promising approach.