Multiple sclerosis (MS) is an inflammatory, demyelinating disease in the central nervous system (CNS) affecting approximately 0.1% of the population in the northern part of the world. The factors behind the initiation of the inflammatory response are not known at present, but MS is considered as a complex disease depending on genetic as well as environmental factors. Experimental autoimmune encephalomyelitis (EAE) is the prevailing experimental rodent model for multiple sclerosis (MS). Disease is induced in genetically susceptible mice or rats by immunization with myelin proteins or peptides, which leads to an infiltration of leukocytes into the CNS. EAE has been subjected to investigations of genetic susceptibility to disease development. By the identification of genes predisposing to EAE, the hope is to get clues as to what genetic elements are also important in MS. To date, more than 25 Eae loci have been described in the mouse. The quantitative trait loci are linked to different disease traits and several show sex specificity. Here we discuss the current state of the genetics controlling susceptibility to EAE.