The 'hygiene hypothesis' suggests that the decreasing incidence of infections in western countries and developing regions is linked to the rising incidence of autoimmune and allergic diseases. This hypothesis is supported by epidemiological data, particularly migration studies, which show that individuals moving from low-incidence to high-incidence countries acquire immune disorders more frequently in the first generation. Animal models and intervention trials in humans provide evidence for the causal relationship between reduced infection levels and increased immune disorders. The underlying mechanisms include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These changes may be partly due to shifts in microbiota caused by lifestyle modifications, particularly in inflammatory bowel diseases. The review discusses recent epidemiological and immunological data, clinical studies, and the potential therapeutic implications of the hygiene hypothesis.The 'hygiene hypothesis' suggests that the decreasing incidence of infections in western countries and developing regions is linked to the rising incidence of autoimmune and allergic diseases. This hypothesis is supported by epidemiological data, particularly migration studies, which show that individuals moving from low-incidence to high-incidence countries acquire immune disorders more frequently in the first generation. Animal models and intervention trials in humans provide evidence for the causal relationship between reduced infection levels and increased immune disorders. The underlying mechanisms include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These changes may be partly due to shifts in microbiota caused by lifestyle modifications, particularly in inflammatory bowel diseases. The review discusses recent epidemiological and immunological data, clinical studies, and the potential therapeutic implications of the hygiene hypothesis.