This review describes the recent literature on microbial exposures and protective effects for asthma and atopy. Certain microorganism-associated molecular patterns have been identified as agents that might influence the development of the immune system, which in turn leads to protective effects for asthma and atopy. Endotoxins from gram-negative bacteria were the first agents associated with a reduced risk for asthma and atopy. In later studies, β(1→3)glucans, extracellular polysaccharides, and muramic acid from, respectively, molds and gram-positive bacteria were associated with a reduced risk of allergy and asthma separately in rural and urban populations. These results already suggested that not just one but several independent microbial signals from gram-negative and gram-positive bacteria, as well as molds, might play a role in explaining the protective effects. Recently, the diversity of microbial exposure has been associated with such a reduced risk in farmers’ children. Surprisingly, the diversity of both fungal and bacterial exposure seemed to have protective effects. These results open new areas of research and create complex challenges. Methodological issues, such as environmental exposure characterization and assessment and elucidation of potential underlying mechanisms, are discussed because these aspects have a major influence on how microbial diversity can be studied in future studies in relation to protective effects for asthma and atopy.