The hygiene hypothesis states a relationship between the rise of prevalences in allergic diseases and chronic inflammatory disorders on one side and decreased contact with micro-organisms, parasites or their derivatives. It is postulated that the immunologic system has evolved to foresee a massive contact with these biological agents and is now dependent on them. Modern life-style is associated with an elevated hygiene level. Here, we review epidemiological and experimental studies which support the hygiene hypothesis in order to finally describe an immunological model, which explains the implicated mechanisms. The application of the hygiene hypothesis could result in new therapeutic strategies.