The evolutionary relationships between ,, ,, ,, and are poorly understood. In order to further explore the evolutionary boundaries of and compare potential taxonomic solutions for this diverse group and its relatives, we conducted phylogenetic analyses of DNA sequence data from alcohol dehydrogenase (1-I2), beta fibrinogen (-I7), interphotoreceptor retinoid-binding protein (3), and cytochrome- (). Phylogenetic analyses of mitochondrial and nuclear genes produced similar topologies although levels of nodal support varied. The best-supported topology was obtained by combining nuclear and mitochondrial sequences. No monophyletic clade was supported. Instead, support was found for a clade containing, ,, ,, and suggesting paraphyly of and confirming previous observations. Our analyses indicated an early divergence of from (approximately 8 million years ago), whereas most other peromyscine taxa emerged within the last 6 million years. To recover a monophyletic taxonomy from and affiliated lineages, we detail 3 taxonomic options in which, ,, , and are retained as genera, subsumed as subgenera, or subsumed as species groups within . Each option presents distinct taxonomic challenges, and the appropriate taxonomy must reflect the substantial levels of morphological divergence that characterize this group while maintaining the monophyletic relationships obtained from genetic data.