In addition to genetics, several environmental variables appear to impact allergic risk. Meta-analyses of epidemiologic studies presented in this article demonstrate a correlation between specific ambient exposures (eg, livestock, pets, endotoxin, and unpasteurized milk ingestion) and reduced allergic risk during childhood. Additional laboratory investigations discussed in this review characterized the intrinsic immunostimulatory activities of living environments. Considered together, results of these investigations suggest a novel paradigm by which early-life home exposures to microbial products and other allergen-nonspecific immunostimulants modify allergic risk.