The emergence of pathogenic viruses in new species offers an unusual opportunity to monitor the coadaptation of viruses and their hosts in a dynamic ongoing process of intense biological selection. Tracking lentivirus epidemics in man, monkeys and cats reveals genomic struggles at three levels: quasispecies divergence within an individual; coadaptation of virus and host genomes subsequent to disease outbreaks; and transmission, spread and pathogenesis in related host species. Aspects of each level are revealed by examining the genetic diversity of feline immunodeficiency virus in domestic and wild cat species. This approach has been facilitated by the recent genetic characterization of a novel lentivirus in lions.