While compliance rates with interferons and glatiramer acetate treatment have been high when assessed in the context of controlled clinical trials, we have observed substantially less consistent rates of drug administration in general practice. Correspondingly, the magnitude of drug efficacy achieved on clinical and surrogate markers of disease activity in the latter patient group may be compromised compared to patients participating in controlled clinical trials. Further, in many circumstances, the perception of breakthrough disease simply constitutes treatment noncompliance.