Achieving optimal patient benefit from biological therapies can be hindered by drug instability, rapid clearance requiring frequent dosing or potential immune reactions. One strategy for addressing these challenges is drug modification through PEGylation, a well established process by which one or more molecules of polyethylene glycol (PEG) are covalently attached to a biological or small-molecule drug, effectively transforming it into a therapy with improved pharmacokinetic and pharmacodynamic properties. Numerous PEGylated therapeutics are currently available, all of which have at least comparable efficacy, safety and tolerability to their unmodified forms. A PEGylated form of interferon-β-1a (PEG-IFNβ-1a) is being developed to address an unmet medical need for safer, more effective and more convenient therapies for multiple sclerosis (MS). Phase I study data suggest that PEG-IFNβ-1a should provide patients with a first-line therapy with a more convenient dosing regimen while maintaining the established efficacy, safety and tolerability of presently available IFNβ-1a. The ongoing global ADVANCE phase III study will determine the clinical efficacy of PEG-IFNβ-1a in patients with relapsing MS.