Interferon-beta is an established therapy in relapsing-remitting multiple sclerosis. Recently, it has also been shown that interferon-beta-1b is effective in secondary progressive multiple sclerosis. However, adverse effects of interferon-beta treatment are common, particularly during the first weeks of treatment, and are a major concern. Flu-like symptoms, injection site reactions and laboratory abnormalities are the most common adverse effects, and may result in reduced compliance or even discontinuation of treatment in a number of patients. Therefore, efforts to minimise these reactions, e.g. appropriate comedication with analgesic/antipyretic drugs, use of correct preparation and injection technique and sometimes modification of the dosage of interferon-beta, are of considerable importance. This article provides an overview of the management of clinically relevant adverse effects related to treatment with interferon-beta, based on a literature review and personal experience. Essential aspects of patient information are also stressed. If these recommendations are followed, adverse effects related to interferon-beta may be substantially reduced in the majority of patients.