The interior of the Guiana region in north‐eastern South America was one of the last mountain areas to be explored in the Americas; the flat and rocky summit of Roraima was ascended for the first time only in 1884. This is one of more than 60 such table mountains, called tepuis by the local indigenous inhabitants. Most of these mountains and mountain ranges, distributed over the still largely inaccessible interfluvium between the Amazon and Orinoco rivers, have now been identified and mapped. Some have been partially explored scientifically, but the majority are still virtually unexplored. The geology, hydrology, climate, biodiversity, contemporary and evolutionary biology and exploration of the region are discussed in this chapter. Four different age groups of sandstone plateaus occur in the region: the Roraima tepuis, the Neblina tepuis, the Tunuí sandstone plateaus and the Chiribiquete–Araracuara sandstone plateaus. The latter are located in Colombia, while the first three are mainly found in Venezuela and adjacent Brazil and Guyana. The relatively isolated mountain summits of the Guiana tepuis above ~1500 m form the Pantepui Province of the Guiana biogeographical region, one of the most biologically interesting bioregions of the Neotropics. This province harbors an assemblage of highly characteristic biota: the flora consists of almost 130 plant families with 336 (including 61 endemic) genera and over 2100 (with almost 1300 endemic) species, which are distributed in several floristic areas. The animal life – of which birds, mammals, frogs and lizards are the best known – is characterized by similarly high levels of endemicity, in spite of relatively low population densities, probably due to the low nutrient contents of the dominant plant groups. Recent genetic studies show that diversification of this rich and endemic biota, once thought to have taken place in nearly complete isolation, is in fact characterized by sparse but continuous biotic interchange with other regions and ecosystems in South America. In this sense, the Guiana Highlands have functioned both as a source and a sink of diversity to the rest of the continent. Although some of the lineages colonizing the tepuis were pre‐adapted to the mountain environment, most had to develop features to cope with the novel ecological conditions encountered. Phylogenetic analyses further show that current diversity may be underestimated, with both well‐differentiated and cryptic species awaiting discovery. @en