Human endogenous retroviruses (HERVs) are ancient retroviral DNA sequences whose expression plays important roles in mammalian physiological processes such as syncytium formation during pregnancy or brain development. Aberrant expression of HERVs is associated with neurological disease, with cause/effect relationships in multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Environmental factors, viral infections included, alter their tight epigenetic control. For example, some HIV patients develop HIV-associated ALS (HALS). Importantly, antiretroviral therapy relieves ALS symptoms at the time that reduces HERV-K expression. Furthermore, in vitro experiments show that FDA-approved anti-HIV drugs are effective at reducing HERV-K expression in HIV-negative ALS patients. Thus, two clinical trials testing antiretroviral therapy in ALS patients are ongoing (NCT02868580 and NCT02437110). In addition, a monoclonal antibody targeting the envelope protein (Env) of the human endogenous multiple sclerosis-associated retrovirus, HERV-W, called GNbAC1 or Temelimab, has been developed by the Swiss company GeNeuro. The results for the clinical trials NCT02782858 and NCT03239860 seem encouraging. This poster summarizes the epigenetic mechanisms controlling HERV expression, the relationship of their activation with inflammatory processes and the clinical trials directed at regulating aberrant HERV expression in MS and ALS.