Multiple sclerosis (MS) is a complex neurological disorder characterized by inflammation and degeneration of the central nervous system, primarily involving the white matter. On the basis of a wide body of evidence in experimental models and in affected patients, several attempts to treat MS using drugs which modulate immune reactions have been performed or are currently ongoing. However, it should be stressed that inflammation does not have only a detrimental effect in MS. In fact, parts of the inflammatory events are crucial for the control and conclusion of the acute phase of damage and it is probable that they actually favor regeneration and recovery. Due to the above, several trials with immunosuppressant drugs failed or were suspended because of unexpected worsening of the course of MS. The knowledge of MS immunopathogenesis is so rapidly evolving that any attempt to review it is in some way frustrating. On the other hand, this evolution is at the basis of the several new treatment options which can be hypothesized for this disease. The current status of immunosuppression in MS and the possible future development of MS treatment will be reviewed, with particular reference to those treatments which have already been tested in clinical trials and which are based on sound evidence of a putative interference with specific events occurring in MS, with the sparing of general immunity.