Multiple sclerosis (MS) is an autoimmune disease characterized by areas of inflammation, demyelination and axonal damage. The etiology of MS is multifactorial with an interaction between genetic, environmental and geographical factors. The objective of this study was to review the physiopathology and the genetic polymorphisms associated with the development and clinical course of MS. Studies carried out in populations worldwide showed that polymorphisms in the genes of the major histocompatibility complex (MHC) class II and class III have been associated with susceptibility, resistance and clinical forms of MS. Considerable attention has been focused on studies evaluating disease-modifying effects in MS that identified seven genes of probable importance such as the HLA class II, ApoE, IL-1ra, IL-1β, TNF-α, TNF-β and CCR5 genes. However, the results described in the literature about genetic biomarkers in MS are not consistent in the worldwide population. The detection of a single nucleotide polymorphism involved in the etiology and physiopathology of MS is very difficult and, it is likely that, several genetic polymorphisms are involved, each with a small contribution to the susceptibility or resistance to MS. Taken together the results show the need for continued research in genetically heterogeneous populations to identify new biomarkers associated with MS that could be used as prognostic markers or as therapeutic targets to modulate the autoimmune response in MS patients. This information may contribute to a better understanding of the physiopathology and treatment of MS, with the possibility of developing different therapeutic strategies according to the genetic profile of each individual.