Subcutaneous recombinant interferon-β-1a (Rebif®) 22 or 44µg three times weekly is a valuable option in the first-line treatment in patients with relapsing-remitting multiple sclerosis. It has shown benefits on outcome measures related to relapses, progression of disability, and magnetic resonance imaging in clinical trials. A significant efficacy advantage for subcutaneous interferon-β-1a three times weekly over intramuscular interferon-β-1a 30µg once weekly was shown at 24 and 48 weeks. The most common adverse events are generally mild and clinically manageable. Considering both direct and indirect comparative clinical trial data, an assessment suggests that subcutaneous interferon-β-1a 44µg three times weekly has the best benefit-to-risk values of the available disease-modifying drugs used to treat relapsing-remitting multiple sclerosis.