Rodent-borne hantaviruses have received considerable attention in recent years due to the high mortality rate in humans that their infections cause. Anthropogenic stressors are key factors in the emergence of hantavirus-associated diseases. Urbanization, deforestation, noise pollution, artificial lighting and electromagnetic fields are the most common forms of human impact on the environment. An increased systemic concentration of the immunosuppressive class of steroid hormone glucocorticoid is a frequent consequence of chronic anthropogenic stress. Elevated glucocorticoid levels play a crucial role in modulating immune tolerance of rodents, thereby enabling establishment of the host-pathogen interaction. Glucocorticoids support virus persistence in the reservoir host by activating an organ-specific regulatory response mediated by T regulatory lymphocytes to reduce inflammatory and antiviral responses, principally via production of cytokines interleukin-10 and transforming growth factor-. In-depth analysis of this mechanism would help to understand how rodents maintain a disease-free condition. This may have implications for a cost-effective intervention strategy against hantavirus and other zoonotic human pathogens.