Viral infections make a natural part of our existence. They can affect us in hundreds of different ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared protecting our vital organs with no other consequences. Sometimes, things go wrong and the reaction of our immune system against the pathogen causes organ damage (immunopathology) or leads to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototype viral systems showing that the interaction of our immune system with the viruses can either accelerate or prevent autoimmunity. Studies using LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established in LCMV are described in this short review.