This chapter discusses the genetics of resistance to virus-induced leukemias. It discusses the genetics of susceptibility to leukemia in mice, the relevance of viruses as etiological agents, and the relationship of this information to leukemias and lymphomas in man. The studies that have formed the foundations of the current knowledge were begun several decades ago, with the period prior to 1960 being characterized by the gradual acceptance of the fact that viruses could cause cancer. The chapter highlights the virology of leukemia-inducing and related viruses, discusses the issues of specificity in virus-host genomic interaction, and describes the current knowledge of host genes conferring resistance or susceptibility to virus-induced neoplasia. The proposition that leukemias are virus induced has been suggested in the studies of the infectious transfer of leukemias in chickens and mice.