The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors. Among the downstream molecules implicated are Jak/Stat, NF-κb, ERK1/2, p38 or Jun/Fos, current MS drugs target some of these pathways. This article will with the aid of the latest research results of systems biology approaches that study pathway dysregulation in the process of MS development, targeting these relevant MS-signaling pathways, offers the opportunity to accelerate the development of novel individual or combination therapies for the future of new drug research.