This chapter focuses on zoonoses transmitted by South American cricetid rodents, with particular emphasis on mammarenaviruses and orthohantaviruses. Regarding the genus Mammarenavirus, viruses of the Tacaribe or New World complex are reviewed, and their natural reservoirs are discussed. Many of these viruses were identified and isolated at a time when the taxonomic classification of the rodents was based solely on morphology and external characters. In recent years, the combination of the classical taxonomic approaches with molecular systematics, biogeography, and ecological niche modeling has led to important changes in the taxonomic identity of many rodent reservoirs. In this chapter, by using available geographical information and taxonomic advances, where appropriate, we give the correct names of rodents, replacing the incorrect original names. With respect to the genus Orthohantavirus, the scenario is more complex in terms of the number of viral variants on the American continent. One of the geographical areas with the greatest viral diversity is the Southern Cone of South America (i.e., Argentina, Chile, and Uruguay). We mention the cases for which reservoirs have been confirmed and the cases for which antibodies have been detected in certain species, but these are probably “spillovers” from horizontal transmissions. In specific cases, the current taxonomic identities of rodents are also questioned.