Archaeology has matured into a well-established discipline, generating new data and contributing theoretical and methodological approaches to various other fields. While archaeology primarily focuses on understanding past socio-cultural human behaviors, many research projects on Pampas hunter-gatherers take an interdisciplinary approach, emphasizing geological, geomorphological, stratigraphical, paleoenvironmental, and palaeoclimatological topics. This interdisciplinary archaeological research has provided crucial data for interpreting the various processes during the Pleistocene-Holocene transition in the Pampas region, where human colonization occurred amidst significant environmental changes. Early archaeological sites have yielded valuable faunal information through zooarchaeological research, which is greatly sought after by biologists and paleontologists. This chapter aims to review and discuss the current state of knowledge and the recently proposed models regarding the interaction between the Pampean hunter-gatherers and the final Late Pleistocene faunal stocks, with a particular focus on the timing and causes of Pleistocene mammal extinctions. The discussion will evaluate models that attribute anthropic actions as the main reasons for extinction and will also consider the probable occurrence of direct and indirect effects on the faunas. Additionally, proposals emphasizing environmental changes and the hypothesis regarding the Holocene survival of Pleistocene species will be explored. The chapter will also analyze the role of the available technology and the likely procurement strategies employed under low demographic conditions to obtain prey (e.g., hunting, scavenging). The available technological systems for the period under consideration will be assessed to determine if they could justify hunting as the primary factor in the Pleistocene faunal extinction. Furthermore, alternative faunal procurement strategies (e.g., scavenging) and subsistence models (e.g., generalized or/and specialized) will be discussed using existing results from zooarchaeology.