Two Old World rodents, house mice (Mus musculus) and Norway rats (Rattus norvegicus), were introduced into and established populations on every continent, save Antarctica. With their travels, they concomitantly introduced several zoonotic agents capable of causing human diseases. Two viruses-Lymphocytic choriomeningitis virus (LCMV; genus Arenavirus with mice) and Seoul virus (SEOV; genus Hantavirus with rats)-can cause chronic infections within their respective rodent hosts, resulting in persistent or lifelong sporadic shedding of virus through secreta and excreta. Although the prevalence of infection within their wild rodent hosts can exceed 25% among mice infected with LCMV and 50% among rats infected with SEOV, acute human disease resulting from direct transmission from wild rodents is rarely reported even though both species live in close coexistence with humans. The usual "classic" zoonotic cycle of transmission from wild rodent reservoirs to humans now includes multiple unusual/unexpected routes. The largest described outbreaks of human disease caused by these viruses are linked to pet rodents. A novel reservoir host, the golden hamster, has supplanted house mice as the major source of LCMV infection, and SEOV outbreaks are linked to fancy rats kept as pets. Following LCMV, and to a lesser extent SEOV, outbreaks or infections associated with lab animals and/or cultured tissues derived from mice and hamsters have led to hundreds of cases of LCMV among laboratory workers, and SEOV has been detected among cell-cultured tissues. Additionally, LCMV is now a recognized source of severe congenital disease and is the unexpected source of severe and often fatal disease among solid organ recipients. Although the extensive usual and unusual routes of LCMV infection are exceptional there are many parallels with SEOV emergence.