Abundant Late Pleistocene bone assemblages were recovered at a number of cave sites located at Ultima Esperanza, South Chile. Some of these sites also include indications of ephemeral occupations by Late Pleistocene human foragers, particularly at Cueva del Medio and Cueva Lago Sofia 1. This evidence suggests different degrees of interaction with extinct faunas. Our excavations and dating program shows that Ultima Esperanza was occupied by extinct mammals at least since ca. 17,000 Cal BP, shortly after the retreat of the Late Pleistocene glaciers. The main species present in these sites are Mylodon darwini, Hippidion saldiasi and several extinct camelids and carnivores. Our recent work at Cueva Chica, Cueva del Medio and Cueva del Milodon uncovered evidence of Late Pleistocene periglacial/paraglacial features which suggest the presence of a very cold environment, evidence that is in agreement with recently published palynological information. Our studies of the bone assemblages suggest that Cueva del Milodon and other large caves were used as ground sloth lairs, while several endogene caves were used as carnivore lairs, particularly by Panthera onca mesembrina. However, most of the sites are temporal palimpsests in which a taphonomic approach was used to try to isolate the main depositional agents. The extinction of most of the taxa recovered at these sites is discussed in the light of the most recent paleoenvironmental evidence.