At present, the pathophysiology and specific biological markers reflecting pathology of multiple sclerosis (MS) remain undetermined. The risk of developing MS is considered to depend on genetic susceptibility and environmental factors. The interaction of environmental factors with epigenetic mechanisms could affect the transcriptional level and therefore also the translational level. In the last decade, growing amount of hypothesis-free ‘omics’ studies have shed light on the potential MS mechanisms and raised potential biomarker targets. To understand MS pathophysiology and discover a subset of biomarkers, it is becoming essential to take a step forward and integrate the findings of the different fields of ‘omics’ into a systems biology network. In this review, we will discuss the recent findings of the genomic, transcriptomic and proteomic fields for MS and aim to make a unifying model.