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Many physiological and anthropological studies have investigated the unique Andean and Himalayan populations that have resided for many hundreds of generations at high altitude (HA). A nonscientific survey of the extant literature reveals a relatively liberal tradition of inferring genetic (evolutionary) adaptation to HA in these groups, often based on limited evidence and/or based on study designs insufficient to fully address the issue. In order to provide some perspective, I review relevant methodological issues that should be considered before evolutionary inference is made. On the whole, this paper takes a conservative stance and cautions against evolutionary inference based on the serious limitations of currently applied research approaches.