The diversity of habitats as a consequence of the Andes uplift resulted in physiographic heterogeneity, creating a variety of microclimates that have induced different adaptive or plastic responses, resulting in biodiversity hotspots. Thus, Andean lizards experience thermal and moisture gradients that pose challenges and opportunities leading them to inhabit suboptimal ecological and physiological conditions or promote the invasion into novel niches. During the last 11,500 years, these environments in the Andes have been drastically modified by acute and chronic disturbances such as volcanic eruptions, prolonged droughts, fires, and climate change. Recent projections indicate a threat to high-altitude Andean biodiversity due to reduced water availability, land degradation, and desertification. The high elevations present inhospitable conditions, especially for oviparous species, while the viviparous reproductive mode would have played a key evolutionary role in the radiation related to the ability to colonize environments at high altitudes. In particular, oviparous lizards at low elevations exhibit low thermal niche buffers, while viviparous lizards are less vulnerable to climate change than most lizard families worldwide. Regarding climate change, the differences between slow and faster life cycles could be vital to allow adaptive responses to counteract changes in habitat suitability and fragmentation that isolate populations and increase their vulnerability in the coming decades. Herein, we summarize the last three decades of integrative research conducted by the Laboratory of Ecophysiology and Life History of Reptiles (Instituto de Investigaciones en Biodiversidad y Medioambiente, Consejo Nacional de Investigaciones Científicas y Técnicas—Universidad Nacional del Comahue) in San Carlos de Bariloche, Río Negro Argentina. This body of research provides crucial insights into how Andean lizards may persist, adapt, or decline in response to ongoing and future environmental changes, highlighting the importance of ecophysiological and life-history traits in shaping their resilience and evolutionary trajectories.