The Atacama Desert, Central Andes of Northern Chile, is an extreme environment characterized by high UV radiation, wide temperature variation, minimum precipitation and is reputed as the driest desert in the world. Scarce lagoons associated with salt flats (salars) in this desert are the surface expression of shallow groundwater which serve as refugia for life, and often host microbial communities associated with evaporitic mineral deposition. Recent investigations of the Puquios of the Salar de Llamara in the Atacama Desert based on multidisciplinary field studies provide unprecedented detail regarding the spatial heterogeneity of physical, chemical, and biological characteristics of such saline lake environments. Four main lagoons (‘Puquios’) and more than 400 smaller ponds, occur in an area less than 5 km2, are characterized by high variability in electrical conductivity, benthic and planktonic biota and microbiota, lagoon bottom type, and style of mineral deposition. The heterogeneity of system parameters as observed spatially in the Puquios is likely to be expanded with temporal observations incorporating seasonality. Results provide new insight into the complexity of these Andean ecosystems, which may be key to resilience in extreme environments at the edge of habitability.