Interferon (INF) beta 1a 22 or 44 mug (Rebif((R))) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF beta 1a 22 or 44 mug s.c. t.i.w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs beta in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif((R)). Additional evidence indicated a beneficial effect of INF beta 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically definite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefits on relapse- and MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF beta 1a 22 or 44 mug s.c. t.i.w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable.