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High-altitude areas are important socio-economical habitats with ruminants serving as a major source of food and commodities for humans. Living at high altitude, however, is extremely challenging, predominantly due to the exposure to hypoxic conditions, but also because of cold temperatures and limited feed for livestock. To survive in high-altitude environments over the long term, ruminants have evolved adaptation strategies, e.g. physiological and morphological modifications, which allow them to cope with these harsh conditions. Identification of such selection signatures in ruminants may contribute to more informed breeding decisions, and thus improved productivity. Moreover, studying the genetic background of altitude adaptation in ruminants provides insights into a common molecular basis across species and thus a better understanding of the physiological basis of this adaptation. In this paper, we review the major effects of high altitude on the mammalian body and highlight some of the most important short-term (coping) and genetically evolved (adaptation) physiological modifications. We then discuss the genetic architecture of altitude adaptation and target genes that show evidence of being under selection based on recent studies in various species, with a focus on ruminants. The yak is presented as an interesting native species that has adapted to the high-altitude regions of Tibet. Finally, we conclude with implications and challenges of selection signature studies on altitude adaptation in general. We found that the number of studies on genetic mechanisms that enable altitude adaptation in ruminants is growing, with a strong focus on identifying selection signatures, and hypothesise that the investigation of genetic data from multiple species and regions will contribute greatly to the understanding of the genetic basis of altitude adaptation.