Background: Immunomodulatory therapies are widely used in adults with multiple sclerosis (MS) and safety and tolerability is well-established. Although at least 5% of all patients with MS experience the clinical onset of their disease prior to age 18 years, the available literature on safety and tolerability of immunomodulatory therapies for pediatric-onset MS is limited. Methods: The authors retrospectively reviewed safety and tolerability of interferon beta-1b (IFN beta-1b) in a cohort of 43 children and adolescents treated for a mean of 29.2 months (SD 22.3 months). Results: Mean age at start of IFN beta-1b treatment was 13 years. Eight children were <= 10 years. Most common adverse events included flu-like syndrome (35%), abnormal liver function test (26%), and injection site reaction (21%). No serious or unexpected adverse events were reported. Conclusions: Although data on long-term effects on the maturing organ systems are lacking, the safety profile supports the safety and tolerability of interferon beta-1b (IFN beta-1b) in children with multiple sclerosis and related diseases. All patients treated with IFN beta-1b should undergo regular monitoring of liver function.