During the last 10 years recombinant interferon-beta-1a administered subcutaneously has been the subject of several clinical trials in relapsing remitting multiple sclerosis (RRMS), in secondary progressive MS (SPMS), as well as in clinically isolated syndromes. All of them met the criteria of evidence level class I. Consistent evidence for moderate immunomodulatory effects on clinical parameters of disease activity was gained, and even higher efficacy of IFN-beta-1a sc. on MRI activity of multiple sclerosis was proven. Indirect evidence confirmed the hypothesis of a dose-response curve for IFN-beta-1a formulations in MS. The higher efficacy of IFN-beta-1a 44 microg sc. TIW, however, also includes more adverse events such as injection site reactions, flu-like symptoms and a moderate immunogenicity. Current evidence does not allow a recommendation of IFN-beta-1a sc. as most effective first line therapy, because also the individual patient's choice in the route of administration and long-term effects of neutralizing antibodies to IFN-beta-1a sc. must be taken into account. In the long-term, IFN-beta-1a showed a beneficial safety-tolerability profile with 50 % of patients sticking to the initial immunomodulatory treatment. There were no teratogenic effects, IFN-beta-1a sc. did not enhance depressive symptoms. Data on inhibition of the progression of disease, however, remained inconclusive. Probable beneficial effects of IFN-beta-1a sc. on cognitive function or "chronic fatigue" have not been investigated yet.