The study by Zhao and colleagues, in this issue of Cancer Research, builds on previous work where they showed that transient activation of Hedgehog signaling within the murine submandibular gland rescued radiation-induced salivary gland dysfunction. The current study provides mechanistic insight into this phenomenon by showing that restoration of radiation-depleted resident macrophages through prorepair paracrine interactions with endothelial cells and epithelial progenitors rescued salivary function.See related article by Zhao et al., p. 5531.