Multiple sclerosis (MS) is an inflammatory disease of the CNS. The clinical presentation of MS is heterogeneous. Interferons (IFNs) were the first agents to show clinical efficacy in the treatment of MS and prolonged treatment is still the best available therapy. Although IFN treatment ameliorates immune dysfunction, the response is partial. Clinical experience indicates that there are responders and nonresponders. This distinction suggests that a subset of patients are insensitive or resistant to the action of IFN. This implies that pharmacodynamic responses may differ between patients, leading to interindividual differences in clinical response. Understanding of the factors that underlie the therapeutic response is key to the identification of predictive markers. Here, we describe novel developments in pharmacogenomics research to improve the understanding of the pharmacological effects of IFN therapy, and the identification of biomarkers that allow stratification of MS patients for their response to IFN-beta. Ultimately, this information will lead to a personalized form of medicine, whereby a specific therapy will be applied that is best suited to an individual patient.