In humans, exogenous retroviruses are known to cause immunodeficiency and neurological disease. While endogenous retroviruses are firmly established pathogens in other species, the human endogenous retroviruses (HERVs) may well be considered as emerging pathogens. HERVs also exhibit complex interactions with exogenous retroviruses and herpesviruses. Two neurological disorders in particular are associated with HERVs: multiple sclerosis (MS) and schizophrenia. HERV-H/F and HERV-W are specifically activated both in the circulation and the central nervous system (CNS) in a majority of MS patients, and particularly, the envelopes (env transcription and Env proteins) appear strongly associated with disease activity. Interferon beta (IFN-beta) therapy is well-established for MS. IFN-beta is also known to have anti-retroviral activities toward exogenous retroviruses (HIV and HTLV-I). New reports show that IFN-beta also mediate down-regulation of HERV-H/F and HERV-W in MS patients. HERV-W and HERV-K transcription (gag and pol) appears, to some extent, to be up-regulated in the circulation and the CNS of patients with schizophrenia. The expression of anti-HERV-W Gag reactive epitopes is reported to be down-regulated in the brain but up-regulated in the blood from schizophrenia patients. The pathogenic potential of HERVs certainly merits further studies.