This article reviews the most relevant data regarding evidence of stress and disease in native populations from Southern Patagonia and proposes future directions for paleopathological research. It focuses on the disease patterns in hunter-gatherer societies and the changes produced by contact and colonization. Studies of oral pathologies show a high frequency of dental attrition and low frequency of caries and antemortem tooth loss. Individuals with terrestrial dietary patterns show evidence of higher mechanical stress in the spine than those who participated in marine economies, based on the prevalence of Schmorl's nodes and vertebral osteophytosis. Porotic hyperostosis is more prevalent in individuals who had a marine diet and is probably related to nutritional impairment and parasitic infections. A higher frequency of metabolic stress was identified in individuals who lived in missions, perhaps because of declining quality in diet, hygiene, and living conditions. Paleoparasitological studies identified several species of parasites associated with human skeletons and terrestrial fauna. Moreover, recent studies suggested that treponematosis and tuberculosis were present in Patagonia since at least 1000 years BP. Future paleopathological research should increase the size and quality of studied samples and apply new methods and interpretive criteria. Detailed research into infections, degenerative joint diseases, and trauma (including violence episodes) has rarely been conducted.