Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS.