Comprising >240 extant species, Macrobrachium Bate, 1868 is the most speciose caridean genus in Palaemonidae. It is generally considered as a monophyletic clade that lives exclusively in limnic and brackish habitats. Thus, it may provide a suitable model for the reconstruction of evolutionary transitions of euryhaline shrimp from ancestral state of living in the sea towards invasions of freshwater environments. Reviewing patterns of the biology (adaptative physiological and reproductive traits) and modern biogeographic distribution of this clade, I propose here a scenario for its tentative origin and evolutionary invasion of limnic inland waters, especially in the Americas. Macrobrachium shows: 1) a world-wide tropical to subtropical distribution, with only few species occurring in temperate regions and none in cold waters at high latitudes; 2) a clear preference for low salinity conditions (based on strong osmoregulatory capacities); 3) larval export strategies in coastal species (with diadromous migrations and invariably an extended larval development in estuaries); and 4) almost exclusively an abbreviated and lecithotrophic mode of larval development in hololimnetic inland species. 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), inWest Africa, and in the Americas. In a clade with common ancestry, this pattern can only be explained with a Tethyan origin and dispersal. Hence, I suggest an origin of ancestral Macrobrachium in theMesozoic. As a consequence of the breakup of Gondwana and fragmentation of the Tethys Sea, mainly during the Late Cretaceous and Palaeogene, Neotropical and West African clades became isolated from the remaining congeners and thus can be considered as Tethyan relicts. In the Neotropics, the closure of the Central American landbridge in the Late Pliocene was a significant vicariant event that caused diversification of coastal Macrobrachium in the Caribbean region, so that two separate groups of extant species live now in the Atlantic and Pacific drainage systems. The distribution of hololimnetic inland species can be explained by continental floodings occurring during the Miocene sea level highstand. Due to concomitant sub-Andean subsidence and impounded by the uplift of the Andes, the huge Pebas wetland system was formed at that time, covering the vast proto-Amazonas-Orinoco catchment area with sub-Andean lowlands reaching from Columbia to southern Bolivia. This allowed for incursions of marine-derived lineages of euryhaline shrimp and other coastal animals throughout northern and central South America, followed by adaptive radiations in freshwater. After the breaching of the continental divide (mainly the Purus Arch) in central Amazonia, probably in the Late Miocene, the modern eastward flow of the Amazon developed, draining to the Atlantic Ocean. Fluctuation but trending to a general decrease in global sea levels during the Pliocene and Pleistocene caused fragmentation of previously interconnected inland waters, promoting vicariant diversification of hololimnetic lineages. However, some hydrological connections between different catchment areas remained transitorily open, providing limited dispersal routes that also may have influenced speciation, e.g., through hybridisation. Thus, the modern distribution patterns of Neotropical Macrobrachium reflect interacting effects of tectonic events including Andean orogeny and the closure of the Panamaian landbridge, Miocene marine incursions, and possible cross-drainage dispersal through historical connections between river basins.