The development, progression, diagnosis and treatment of autoimmune diseases, such as multiple sclerosis (MS), are convoluted processes which remain incompletely understood. Multiple studies demonstrated that the interleukin (IL)-2 - IL-2 receptor (IL-2R) pathway plays a pivotal role within these processes. The most striking functions of the IL-2 - IL-2R pathway are the differential induction of autoimmune responses and tolerance. This paradoxical function of the IL-2 - IL-2R pathway may be an attractive therapeutic target for autoimmune diseases such as MS. However, the exact mechanisms that lead to autoimmunity or tolerance remain to be elucidated. Furthermore, another factor of this pathway, the soluble form of the IL-2R (sIL-2R), further complicates understanding the role of the IL-2 - IL-2R pathway in MS. The challenge is to unravel these mechanisms to prevent, diagnose and recover MS. In this review, first, the current knowledge of MS and the IL-2 - IL-2R pathway are summarized. Second, the key findings of the relation between the IL-2 - IL-2R pathway and MS have been highlighted. Eventually, this review may launch broad interest in the IL-2 - IL-2R pathway propelling further research in autoimmune diseases, including MS.