The 'hygiene hypothesis' was first proposed by Strachan in 1989 suggesting that infections and unhygienic contact with older siblings or through other exposures may confer protection from the development of allergic illnesses. This hypothesis has evolved in various ways exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and their effect on underlying responses of innate and adaptive immunity. So far a truly unifying concept is still lacking, but various pieces of a complex interplay between a host's immune response, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures become apparent. All these pieces eventually assemble to the clinical presentation of a complex syndrome namely of asthma and allergic illnesses. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future based on the concepts of the 'hygiene hypothesis'.