Here, we present a comprehensive phylogenetic analysis based on nuclear and mitochondrial DNA sequences of rodents of the subfamily Sigmodontinae. The emphasis is placed on the large tribe Phyllotini; sampling includes for the first time in any molecular-based phylogenetic analysis representatives of several genera traditionally considered to be phyllotines. Given the broad taxonomic sampling, results provide substantial improvements in our knowledge on both the structure of the sigmodontine radiation and of phyllotine phylogenetic relationships. For instance, the tribe Ichthyomyini was not recovered monophyletic. Similarly, in a novel hypothesis on the contents of the tribe Phyllotini, it is shown that unlike Galenomys, the genera Chinchillula, Neotomys and Punomys are not phyllotines. The later genera together with Andinomys, Euneomys, Irenomys and Juliomys form part of novel generic clades of mostly Andean sigmodontine rodents. More in general, results strongly suggest the occurrence of several instances of putative morphological convergence among distinct sigmodontine lineages (e.g. among now considered to be ichthyomyines; between Phyllotini and some Andean taxa; among Euneomys-Neotomys and Reithrodon). Finally, we suggest that the historical biogeography of the sigmodontine rodents is far more complex than earlier envisioned.