Interferon-beta (IFN-beta) is routinely prescribed as an immunomodulatory treatment for multiple sclerosis (MS), but is associated with variable clinical efficacy. Ideally an early predictor of response status would allow more rational provision of this therapy. Both pharmacogenomic and expression analysis have highlighted IFN-beta regulated genes which may influence treatment efficacy. In this review we have summarized and discussed the main genes identified by these studies in MS patients, and supplemented this with data from similar studies of Type I IFN treatment in hepatitis.