Immunoglobulin G (IgG) replacement therapy for primary immunodeficiency disorders is typically administered intravenously (IV) or subcutaneously (SC). The SC route offers the advantages of a reduced risk of systemic side effects and more steady IgG levels. However, SC IgG (IGSC) must pass through the interstitial matrix of the skin, which restricts drug flow and, therefore, the amount that can be administered by local infusion. A new technique, enzyme-facilitated IGSC, addresses this problem by incorporating the use of rHuPH20, a recombinant hylauronidase that enhances IgG dispersion by counteracting the resistant forces associated with hyaluronan in the interstitial matrix. Both animal and human clinical studies have confirmed that the addition of rHuPH20 to IGSC increases bioavailability while preserving the more favorable safety profile of SC versus IV administration.