The International Union for Conservation of Nature (IUCN) defines as “Data Deficient” (DD) those species for which there is inadequate information on its distribution and/or population status to make a direct, or indirect, assessment of its risk of extinction. Unfortunately, for most policy-makers this category is uninformative, limiting the chances to enact conservation measures or to support additional scientific investigation on these species. In this contribution, we analyze the situation of the DD South American rodents, a diverse array of non-charismatic and poorly known species. First, we compiled a systematic list including all rodent species distributed in South America that are categorized by the IUCN as DD. Individual distributional maps for each species were superimposed on a map of South America divided into hexagonal cells of 1 degree of size. The highest species richness values (i.e., S≥8) correspond to three main areas: (1) western Colombia, (2) Central Ecuador, and (3) north-western Argentina. All these areas are found at or close to the Andes, suggesting that, at least partially, our lack of knowledge of some species could be related to the high diversity of the Andean fauna that in turn remains poorly studied. Over a total of 121 species for which we can calculate or infer their distributional ranges, 94 species (i.e., 77.5%) occupy less than 1% of the total South American surface. More than half of the studied species inhabit tropical forests, while the remaining taxa are mostly found in open to brushy, arid-semiarid to temperate habitats such as deserts, grasslands, and scrublands. Half of the DD species are arboreal or fossorial, two life history strategies that make them more difficult to catch through traditional trapping procedures. We suggest that the rarity of several South American rodents could be the result of a combination of small geographical distributions, their occupancy of poorly sampled mountain or desert areas, and their behavioral characteristics.