Although debate continues, there is agreement that dogs (Canis lupus familiaris) were first domesticated in Eurasia, spreading from there to other parts of the world. However, while that expansion already extended as far as Europe, China, and North America by the early Holocene, dogs spread into (and south of) the tropics only much later. In South America, for example, the earliest well-attested instances of their presence do not reach back much beyond 3000�cal. BC, and dogs were still absent from large parts of the continent—Amazonia, the Gran Chaco, and much of the Southern Cone—at European contact. Previous explanations for these patterns have focused on cultural choice, the unsuitability of dogs for hunting certain kinds of tropical forest prey, and otherwise unspecified environmental hazards, while acknowledging that Neotropical lowland forests witness high rates of canine mortality. Building on previous work in sub-Saharan Africa (Mitchell in Archaeol Res Afr 50:92–135, 2015), and noting that the dog’s closest relatives, the grey wolf (C. lupus) and the coyote (C. latrans), were likewise absent from South and most of Central America in pre-Columbian times, this paper explores instead the possibility that infectious disease constrained the spread of dogs into Neotropical environments. Four diseases are considered, all likely to be native and/or endemic to South America: canine distemper, canine trypanosomiasis, canine rangeliosis, and canine visceral leishmaniasis caused by infection with Leishmania amazonensis and L. colombiensis. The paper concludes by suggesting ways in which the hypothesis that disease constrained the expansion of dogs into South America can be developed further.