Inflammatory demyelinating disease of the central nervous system is one of the most frequent causes of neurological disability in young adults. While in situ analysis and in vitro models do shed some light onto the processes of tissue damage and cellular interactions, the development of neuroinflammation and demyelination is a far too complex process to be adequately modeled by simple test tube systems. Thus, animal models using primarily genetically modified mice have been proven to be of paramount importance. In this chapter, we discuss recent advances in modeling brain diseases focusing on murine models and report on new tools to study the pathogenesis of complex diseases such as multiple sclerosis.