Allergy and asthma are chronic inflammatory diseases that result from complex gene-environment interactions. Recent evidence points to the importance of prenatal and postnatal developmental processes in the maturation of balanced immune responses. Novel data indicate that epigenetic mechanisms contribute to the development of T-helper-cell function. Environmental factors, including diesel exhaust particles, vitamins, and tobacco smoke, operate through such mechanisms. Furthermore, the role of environmental microbes provides another-and maybe an even more important-group of exogenous exposures that operate in this critical time frame. A better understanding of fetal immuno-maturation conditions will provide the basis for the development of novel allergo-protective clinical strategies.