The Himalayan mountain range contains the highest peaks on Earth and has provided a diversity of environments for humans, some of which have required substantial genetic adaptation. I have used a combination of SNP-chip data, genome sequences and functional studies to explore the demographic history, genetic structure and signatures of adaptation in Himalayan populations. Eight hundred and eighty three individuals from 49 different autochthonous groups from Nepal, Bhutan, North India, and the Tibetan Plateau in China were genotyped for ~600,000 genome-wide SNPs. High-coverage whole-genome sequences of 87 individuals from a subset of these populations plus three additional ones were also generated. Himalayan populations share a common genetic component derived from a single ancestral population, followed by the development of local fine structure correlating with language and geographical distribution. I find higher genetic diversification within the Himalayan populations than in the surrounding regions which correlates with the distribution of Indo-European and Tibeto-Burman speakers, suggesting that both language and geography have influenced the genetic structure of these populations. I refined Himalayan population demographic history, using both autosomal and uniparental sequences. Himalayan populations display different proportions of gene flow with neighbouring populations and diverse effective population sizes and split times. The Y-chromosome lineages identified are common in South and East Asia and Tibet, but mostly form distinct clusters in the Himalayas. High altitude adaptation seems to have originated in a single ancestral population and then spread widely in the Himalayan region in the last 5,000 years. Genetic signatures of adaptation to high altitude are observed in the Endothelial PAS Domain Protein 1 gene (EPAS1) and several other known and novel candidates. EPAS1 has previously been reported to be under selection and involved in adaptation to living at high altitudes and was suggested to result from introgression of DNA from an extinct hominin species (Denisovans) into Tibetans. However, functional studies of EPAS1 variants have not been systematically carried out and it is still unknown which variant(s) are responsible for high altitude adaptation and their mechanism of action. I used both in silico and in vitro studies to explore these topics and validate EPAS1 candidate regulatory variants. The introgressed haplotype extends for over 300 kb spanning six genes (EPAS1, TMEM247, ATP6V1E2, RHOQ, CRIPT, PIGF). I optimised a protocol to induce hypoxia in cell lines with and without the Denisovan introgressed haplotype. Preliminary results show that in cell lines without the introgressed haplotype, EPAS1 expression increases under hypoxic conditions, whereas in the cell lines with the introgressed haplotype the expression of EPAS1 remains constant. The most likely functional candidate variants fall in a ~32.7kb region within EPAS1. High altitude adaptation thus seems to be driven by EPAS1 as well as coordinated by other genes involved in the hypoxic response.