Resumen: The Southern Hemisphere, with its geographical and landscape peculiarities, concentrates many hotspots of diverse and extreme environments where microbial life thrives. It includes “pristine” or less anthropogenically impacted environments, such as high-altitude and high-latitude ecosystems, which are highlighted in the content of the Research Topic. Among the former, the Andes plateau hosts ecosystems that are ideal to study the role of environmental factors in shaping microbial life. Physical factors like continuous mixing regime were studied on the zonation of planktonic microbial communities in high-altitude (>4,400 m above sea level m.a.s.l) polymictic tropical lakes. Physicochemical factors such as extreme changes in conductivity, temperature and nutrients were identified as factors accounting for viruses-to-prokaryotes (VPR) spatial and diel dynamics in Salar de Huasco high-altitude wetland (located at 3,800 m.a.s.l).