Comprising >240 extant species, Macrobrachium Bate, 1868 is the most speciose genus in the caridean shrimp family Palaemonidae. It is considered as a monophyletic clade, which lives almost exclusively in brackish and limnic habitats. Thus, it may provide a suitable model for the reconstruction of evolutionary transitions of euryhaline shrimps from ancestral live in the sea towards freshwater. Reviewing patterns of the biology (adaptative physiological and reproductive traits) and modern biogeographic distribution of Neotropical Macrobrachium, I propose a scenario for their tentative origin and evolutionary invasions of rivers and fully limnic inland waters in the Americas. As most typical features, the genus Macrobrachium shows a world-wide tropical-subtropical distribution (only few species occurring in temperate regions), a preference for low salinity conditions (based on strong osmoregulatory capacities), larval export strategies in coastal species (with diadromous migrations and larval development in estuaries), and almost exclusively abbreviated and lecithotrophic modes of larval development in hololimnetic inland species. Considering these general traits as well as palaeogeographic and environmental changes during geohistory, I suggest an early appearance of ancestral Macrobrachium already in the Mesozoic. The extant patterns of geographic distribution of this genus are strikingly disjunct, with completely separate groups of species occurring in the Indo-Pacific region (where maximum diversity occurs), in West Africa, and in the Americas. This can only be explained with a Tethyan origin and dispersal. As a consequence of the Gondwana breakup and fragmentation of the Tethys Sea during the Late Cretaceous and Palaeogene, Neotropical and West African clades were isolated from the remaining congeners, and thus, became Tethyan relicts. The closure of the Central American landbridge in the Late Pliocene was a significant vicariant event in the Neotropic. It promoted the diversification of coastal Macrobrachium in the Caribbean region, so that two almost completely separate groups of extant species occur in the Atantic and Pacific drainages. In northern South America, multiple marine transgressions, in particular during the Miocene sea level highstand, caused continental floodings and consequent invasions by marine-derived lineages of shrimp and other coastal animals, many of which later adapted to freshwater. Due to Subandean subsidence and constrained by the concomitant uplift of the Andes in the Miocene, the huge Pebas lake system was formed, which was partially brackish, draining to the Caribbean. It covered the vast proto-Amazonas-Orinoco catchment areas and the Subandean lowlands ranging from Columbia to southern Bolivia. As a consequence, euryhaline coastal lineages from the Caribbean could extensively disperse and radiate throughout northern and central South America. After the breaching of central Amazonian land barriers such as the Purus Arch, probably in the Late Miocene, the modern eastward running Amazon was created, draining since that time to the Atlantic Ocean. Decreasing global sea levels in the Pliocene and Pleistocene caused partial draining and fragmentation of previously interconnected inland waters, promoting vicariant separation and diversification of hololimnetic lineages, although some hydrological connections between different catchment areas remained seasonally or transitorily open as limited dispersal routes. In conclusion, the modern distribution patterns of Neotropical Macrobrachium living in limnic inland waters reflect interacting effects of marine incursions, tectonic events associated with Andean orogeny, and cross-drainage dispersal through historical connections between river basins.