With a growing number of protein therapeutics being developed, many of them exhibiting a short plasma half-life, half-life extension strategies find increasing attention by the biotech and pharmaceutical industry. Extension of the half-life can help to reduce the number of applications and to lower doses, thus are beneficial for therapeutic but also economic reasons. Here, a comprehensive overview of currently developed half-life extension strategies is provided including those aiming at increasing the hydrodynamic volume of a protein drug but also those implementing recycling processes mediated by the neonatal Fc receptor. Copyright © 2011 Elsevier Ltd. All rights reserved.