Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease.