Multiple sclerosis (MS) is a complex, multifactorial autoimmune disorder of the central nervous system (CNS) that causes inflammation, demyelination and neurodegeneration. The increased prevalence of this disease in Arabian Gulf Countries (AGCs) has captivated the author. The following is a deliberative review of the disease with respect to its molecular basis. Briefly, it considers disease pathophysiology though the molecular composition of the cell; the genome, epigenome and mitochondrial genome; and relates these factors to environmental, etiological factors, including: vitamin D, UVR, EBV infection, smoking and obesity. All in all, this review aims to explain the reasons underlying the increasing prevalence of MS in AGCs.