The genus Proechimys is divisible into four groups of species on the basis of bullar septal patterns. Each of the four groups can be further characterized by distinctive distributions and karyotypes. The subgenus Trinomys and the guatrae species group each are comprised of phylogenetically closely-related species. The semispinosus- and brevicauda-groups, although generally distinctive on the basis of bullar septa, are not phylogenetically equivalent to the first two groups. The brevicauda-group, for example, consists of at least three separate species complexes. The taxonomy used in this report reflects several nomenclatural changes from that used in the recent literature. In addition, previously unreported karyotypes are described for P. quadruplicatus, P. gularis, P. decumanus, P. oris, P. oconnelli, and P. mincae.