Identifying factors that promote host shifts is crucial for understanding the origin and maintenance of biodiversity as well as the emergence of novel infectious diseases. Previous research has demonstrated that the opportunity for cross-species transmission and parasite adaptation can play an important role in determining if and when a host shift occurs. Another possibility is that the genetic basis of infection and resistance, when coupled with the process of coevolution (i.e., coevolutionary genetics), plays a pivotal role in determining when, if ever, a host shift occurs. Here we explore this possibility by developing and analyzing a genetically explicit epidemiological model that allows for coevolution and alternative forms of infection genetics. Approximate analytical solutions to this model demonstrate that infection genetics can influence the likelihood of a host shift. Stochastic simulations confirm the important role of infection genetics but in some cases reveal that coevolutionary dynamics modulate the likelihood of host shifts. Our results demonstrate that predicting host shifts requires a detailed understanding of the underlying genetics of infection and resistance. Thus, identifying the genetic architecture of infection and resistance in real systems is of central importance.