Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting young adults (with a peak of onset between the ages of 20 and 40 years). In 80-90% of cases, it is characterized by an early relapsing-remitting (RR) inflammatory phase, followed by a secondary progressive course in which disability progressively accumulates. Interferon-beta (IFNbeta) therapies represent the first-line treatment of RRMS. There are three IFNbeta formulations currently licensed for RRMS. Two are formulations of INFbeta-1a, one administered at a dosage of 30 mug intramuscularly weekly (Avonex(R)) and the other administered at a dosage of 22 or 44 microg subcutaneously (SC) three times a week (Rebif(R) 22 and 44). The third is a formulation of IFNbeta-1b, administered at a dosage of 250 microg SC every other day (Betaseron(R)). These treatments reduce the frequency of acute relapses and, to a lesser extent, disability progression. However, when starting an IFNbeta therapy, a treatment discontinuation rate ranging from 14% to 44% has to be expected. In a sizable proportion of patients, treatment suspension is caused by the occurrence of adverse effects (most commonly a flu-like syndrome and injection site reactions) and/or poor compliance. Individualized patient education and support are critical to improve adherence to therapy in the long term. Approaches aimed at reducing the proportion of subjects interrupting IFNbeta encompass both pharmacological and non-pharmacological interventions, and may involve several professional figures, such as the neurologist, the psychologist, the pharmacist, the physical and speech therapist, and the nurse. Recently, the development of new IFNbeta formulations, with reduced immunogenic potential, has offered an additional approach to improving patient adherence. Biferonex(R) is a pH neutral and human serum albumin-free IFNbeta-1a. A phase III, 2-year study of the product involving patients with RRMS has been conducted, but the results were not considered conclusive enough to allow approval in Europe. Rebif(R) New Formulation (RNF) is a formulation of INFbeta-1a that is not produced using fetal bovine serum and that does not have human serum albumin as an excipient. The formulation has been approved in Europe and an application for approval has been filed in the US. On the basis of the final analysis of a phase III trial, RNF showed higher tolerability, particularly in terms of injection site reactions, compared with the older formulation. Further studies assessing its usefulness as an alternative therapy for patients who are intolerant of other IFNbeta formulations are required.