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Editor’s Note: Progressive multifocal leuko-encephalopathy (PML) is a very rare de-myelinating condition of the central nervous system caused by the polyomavirus, JC virus. It is usually seen in patients who are severely immunocompromised, typically resulting in an untreatable, often fatal, condition. More recently, PML has been associated with monoclonal antibody treatment and the neurology community has become aware of an association between patients receiving the monoclonal antibody natalizumab for highly active multiple sclerosis (MS) and the development of PML. Natalizumab is directed against the 4 chain of the very-late-antigen-4 (VLA-4) receptor and reduces leukocyte trafficking into the central nervous system (CNS). This reduced imunosurveillance in the CNS is thought to potentially predispose natalizumab-treated patients to reactivation of neuro-virulent strains of JC virus, resulting in PML. The number of natalizumab-associated PML cases remains low; however, this potential risk is a worrying development for patients and treating neurologists. The MS community is therefore examining ways to manage these cases and improve patient surveillance.