The concept of health-related quality of life (QoL) includes physical, psychological,and social aspects. This pertains to consequences of chronic diseases and their therapies beyond biological or pharmacological relations. A considerable amount of literature concerning QoL has been published with regard to neurological and non-neurological entities. This study summarizes data from a study in 717 persons with remitting-relapsing multiple sclerosis (MS). Of them,576 could be reevaluated longitudinally after 1 year of treatment with interferon-beta 1a (44 microg subcutaneous Rebif once weekly). Compared to populations of healthy controls or other patients, considerable reductions in the eight subscales and both physical and emotional sum scales of the German version of the short form of the Rand Health Questionnaire (SF-36) questionnaire were assessed. These reductions were even more pronounced in persons with gait impairments. Most SF-36 scales only modestly correlated to physical disability. This indicates that QoL as reported by patients does not depend solely on the physical symptoms of MS. Most findings remained stable for the study population as a whole during 1 year of therapy, while statistically significant improvements were found in clinical responders as defined in this study (relapse-free, physically stable, stable or improved in physician's judgement). Side effects of therapy were not reflected in lower QoL scale values. Implications of findings for future concepts in MS therapy are discussed.