In 1993, interferon (IFN)-β_1b for subcutaneous injection became the first US FDA-approved immunomodulatory treatment for multiple sclerosis, a chronic inflammatory disease of the CNS. In this review of IFN-β_1b, we first present a short introduction to multiple sclerosis and currently available therapeutics. We then summarize current knowledge about the biochemical structure of IFN-β_1b, as well as pharmacokinetics and pharmacodynamics, including data on putative mechanisms underlying therapeutic as well as adverse effects. Furthermore, a critical review of ongoing and recently published clinical trials investigating IFN-β_1b in multiple sclerosis will be provided. Main topics are: trials investigating IFN-β_1b after a first clinical event, at higher dosages or in comparison to once-weekly subcutaneous IFN-β_1a injections, 16 years of long-term follow-up, IFN-β_1b in Japanese patients, the role of neutralizing antibodies, biomarkers for the prediction of therapy response, IFN-β_1b and pregnancy, and IFN-β_1b treatment of children with multiple sclerosis. Finally, we discuss how novel drugs, especially monoclonal antibodies and orally administered immunosuppressants, might soon challenge the position of this well-established agent on the multiple sclerosis therapeutics market.