Irrespective of improved knowledge of many aspects of atopic diseases, the unfavorable trends in their prevalence particularly among children could not have been reversed. A growing body of evidence suggests that something may lack from our societal affluence that has the capacity to provide protection against the development of atopic diseases. Much attention during the last years has been devoted to the hygiene hypothesis. This review outlines the impact of environment and lifestyle, particularly from the perspective of the East-West gradient, on the development of atopic diseases, with a special emphasis on the hygiene hypothesis in its broadest sense.