The capacity of the skin and other organs to resist infection depends on the innate production of molecules known as antimicrobial peptides. Emerging evidence suggests that some of these peptides are important to immune defense by acting not only as natural antibiotics but also as cell-signaling molecules. In this issue Carretero et al. (2007) expand on these findings by demonstrating that expression of human cathelicidin alters multiple signaling pathways in a keratinocyte cell line and enhances wound re-epithelialization in ob/ob mice.