Porcine reproductive and respiratory syndrome (PRRS) is the most economically important disease in pig populations, worldwide. Current research, both in vitro and in vivo, has failed to provide industry with a reliable or effective method to combat the disease. In this paper the present knowledge of the genetics of the host response to porcine reproductive and respiratory syndrome virus (PRRSV) is reviewed. Special reference is made to clinical signs of disease, in vitro and in vivo studies, and evidence of genetic variation in host response to the disease. It is concluded that although clinical signs are numerous, and in vitro and in vivo studies often fail to yield comparable results, there is sufficient evidence of genetic variation in host responses to infection to examine the possibility of breeding for enhanced resistance or tolerance. Advances in genomics have allowed examination of changes in gene expression in response to infection to be examined in tandem with genomewide linkage disequilibrium scans. These advances could allow the possibility for commercial breeding programs to be established, selecting for PRRS resistance or tolerance. When breeding for resistance to one disease, such as PRRS, it could be postulated that the viral control mechanism being exploited could have beneficial effects on resistance to other viral diseases in pigs if, for example, the mechanisms act on primary immune pathways associated with viral replication. Conversely, however, selection for disease resistance could facilitate an increase in susceptibility to other diseases or a reduction in overall productivity. Extensive data recording may be required to guard against such possibilities. Overall, breeding for disease control in pigs is an underutilized tool that could have desirable long-term effects in breeding programs. More research is needed to examine the possible pathways of PRRS resistance so that viable control methods can be found to ease the disease burden and thus increase animal welfare and economic viability.