Man has moved rapidly from the hunter-gatherer environment to the living conditions of the rich industrialised countries. The hygiene hypothesis suggests that the resulting changed and reduced pattern of exposure to micro-organisms has led to disordered regulation of the immune system, and hence to increases in certain chronic inflammatory disorders. The concept began with the allergic disorders, but there are now good reasons for extending it to autoimmunity, inflammatory bowel disease, atherosclerosis, depression associated with raised inflammatory cytokines, some cancers and perhaps neuroinflammatory disorders such as Alzheimer’s and Parkinson’s. This book discusses the evidence for and against in the context of Darwinian medicine, which uses knowledge of evolution to cast light on human diseases. It is the first book to consider the broader implications of the hygiene hypothesis in areas of medicine where it has not previously been applied. The approach is interdisciplinary, looking at man’s microbiological history, at the biology of the effects of microorganisms on the immune system, and at the implications for chronic inflammatory disorders in multiple organ systems. Finally, the authors describe progress in the exploitation of microorganisms or their components as novel prophylactics and treatments in several branches of medicine.