In this paper, I will review the heterogeneity of CFS/ME, its clinical presentation and triggering factors including Epstein-Barr Virus (EBV) reactivation, CFS/ME as an autoimmune-like disease, Epstein-Barr virus induced (EBI) gene 2 (EBI2) dysregulation in CFS/ME, the “EBI subtype” and the future possibility for therapeutic pharmacological EBI2 antagonism in CFS/ME patients. The gene discussed is GPR183; the disease is myalgic encephalomeyelitis/chronic fatigue syndrome.