After many years of involvement in desalination in many parts of the world, I have come to the conclusion that it is in Latin America, in particular in the Atacama Desert, where modern desalination really started in terms of number and diversity of applications. The country which stands out as the cradle of desalination is Chile. In saying this one must acknowledge that this is true in terms of today’s perspective. In fact the areas of the Antofagasta Desert, where the installation and operation of desalination units started in the middle of the nineteenth century and which are analyzed in this paper, were at first part of Bolivia. Land based applications of desalination stepped up their pace in the late nineteenth century in several parts of the world, but it is only in the stretch of desert along the Pacific coast of Peru, Bolivia and Chile, where there is documented evidence that desalination was already applied in several sectors using all the evaporative processes known at the time, such as single effect and possibly MED machines, and the first wind and solar driven desalination plant known. This latter plant is the famous Las Salinas solar desalination plant, built in 1878, which operated continuously for about 50 years. Early applications, documented starting from 1851, were of several types. For instance desalination ensured fresh water supplies to the ports of Cobija, Tocopilla, Mejillones and Antofagasta along the Atacama Desert through tens of ‘resacadoras’ (distillers), guaranteed continuity of fresh water supplies to steam engines of locomotives along the routes of the rapidly expanding railway network, allowed mining activities in places where it would have been difficult to do so otherwise, like in the guano islands off the coast of Peru, and provided the Chilean army with a strategic advantage in the War of the Pacific. This paper is describing and analyzing these early applications of desalination one and a half centuries after they occurred, at a time when the whole of the Latin America region, but in particular the Atacama Desert again, is experiencing a revival of desalination applications and is attracting the attention of the global desalination community.