One of the most dreaded complications in Multiple Sclerosis (MS) patients treated with natalizumab is the appearance of the Progressive Multifocal Leukoencephalopathy (PML). A 54-year-old Mexican woman diagnosed eight years before with MS, received natalizumab for the last three years. The patient developed PLM that was confirmed by clinical, radiological, blood and CSF tests. Her treatment included methylprednisolone, plasmapheresis, immunoglobulin and mirtazapine. Risks, causes, treatments, preventive measures and opportune diagnosis for these patients are analyzed in this report.