The skin protects the body from microbial pathogens by employing Toll-like receptors (TLRs) and other molecules that recognise pathogen-associated molecular patterns to initiate innate immune responses and to direct subsequent adaptive immunity. But when does the innate immune system in human skin become immunologically competent? On p. 4210, Adelheid Elbe-Bürger and co-workers answer this question by analysing TLR expression and function in human skin. The researchers report that, although prenatal and adult skin express a similar spectrum of TLRs, prenatal, infant and child skin express higher levels of several TLRs (particularly TLR3) than adult skin. Moreover, a synthetic TLR3 ligand that mimics viral double-stranded RNA significantly enhances the secretion of several chemokines and cytokines by keratinocytes isolated from foetal and neonatal donors but not by those isolated from adult donors. Thus, the researchers conclude, human skin exhibits age-related changes in TLR expression and function, and foetal keratinocytes are already endowed with specific immune functions that may protect the developing human body from viral infections.