Hantaviruses are a significant public health threat affecting 200,000 people worldwide annually with a mortality rate of 35-40%. Distribution of rodent host species led to specific geographical pattern of the disease. Old World hantaviruses in Asia and Europe causes hemorrhagic fever with renal syndrome (HFRS) and New World Hantaviruses in the Americas causes hantavirus cardiopulmonary syndrome (HCPS). It has been proposed that the interplay between viral effects and host immune response are contributory to the pathogenesis of hantavirus infection. Impairment of endothelial barrier integrity and capillary leakage is central to hantavirus syndromes, but the mechanism on how the virus causes pathology in the renal and cardiopulmonary systems remain unclear. Performing pathogenesis study has been futile due to lack of experimental disease models. This seminar will focus on the current understanding of hantavirus infection pathogenesis and current surrogate disease models used to study the pathogenesis of hantavirus infection.