Multiple sclerosis (MS) is chronic, inflammatory disease of the central nervous system that mainly affects young adults and is characterized with dissemination of demyelinating lesions in time and space. It is well known that MS is very heterogeneous disease, so biomarkers that would reliably determine disease course, outcome or treatment response in early stages of the disease (preferentially clinically isolated syndrome) are desperately needed. Genome-wide expression analysis represents the profile of all genes in a certain tissue or cell population in a certain time point. Therefore, as the sequence of the human genome is entirely known, it is possible to analyze any given human gene in any given context. This review will discuss results and possible applications of genome-wide expression studies in brain tissue and blood samples of MS patients.