This chapter provides an updated overview of hantaviruses, members of the family Hantaviridae, that cause significant human disease worldwide. The epidemiology and distribution of these viruses highlight the ever-changing intersections between humans and rodents. These viruses have also been found in other species that do not cause human disease. The pathogenic strains cause two main clinical syndromes; hemorrhagic fever with renal syndrome (HFRS), and the more severe hantavirus cardiopulmonary syndrome (HCPS). Both are characterized by an endothelial injury with capillary leak and while they have different target organs of effect, there is some overlap. Despite advances in the diagnosis and management of these disease syndromes, outcomes remain largely unchanged highlighting the importance of disease prevention and the need for further advancements in vaccines and therapeutics.