The airway epithelium serves as a physical defense barrier to the external environment for the underlying tissue and suffers frequent injury. The response to injury is inflammation followed by debris clearance and repair. Although IL-13 is known to be a key cytokine in mediating inflammatory and remodeling responses via signal transducer and activator of transcription 6 (STAT6) and early growth response protein 1 (Egr1), our laboratory has demonstrated that IL-13 is critical to airway epithelial repair via the release of heparin-binding epidermal growth factor (HB-EGF) and activation of epidermal growth factor receptor (EGFR). IL-13 signals through two receptors, IL-13Rα1/IL-4R and IL-13Rα2. IL-13Rα2 has previously been thought to act exclusively as a decoy receptor, however our findings show that IL-13Rα2 can act as a signaling receptor and is involved in mediating airway epithelial repair. Differential signaling via IL-13Rα1 or IL-13Rα2 may determine a remodeling versus repair response to injury in airway epithelium.