The development of high resolution genetic polymorphism markers in human genetics has opened an expansive field that would allow the understanding of genome organization in the context of historic evolutionary events. From a taxonomic perspective, we have applied several different indices of genetic differentiation to the phylogenetic analysis of species of Felidae. The approaches which allow for consensus phylogenetic inference include: (1) allozyme genetic distance; (2) 2 dimensional electrophoresis fibroblast protein genetic distance; (3) albumin immunological distances; (4) DNA-DNA hybridization; (5) mitochondrial DNA-restriction fragment length polymorphism; (6) mitochondrial gene sequence including 16S rDNA, NADH dehydrogenase-2, ATPases, D-loop; (7) nuclear coding gene sequences including MHC-DRB, SRY, ZFX, and ZFY homologues. Similar methodology has been used to detect and characterize phylogenetic clades of feline immunodeficiency virus, known to be widespread among non-domestic cat species. Three distinct clades (A-C) are apparent among African lions, while 18 equally divergent clades were seen among pumas. No immune deficiency disease is apparent among wild cat species, although FIV causes AIDS in domestic cats. A dramatic emergence of a novel morbillivirus, related to canine distemper, was observed in the Serengeti lion population in 1994, and this outbreak caused neurologic disease and mortality among over one thousand animals. Feline short tandem repeat (STR) loci were employed to characterize historic subspecies phylogeographic partitions among leopards, pumas, and tigers, as well as for genetic individualization in a forensic homocide case.