The Casiquiare River is a natural channel that connects two of the greatest rivers in the world, the Orinoco and the Amazon in the South American Continent. The aim of this paper is to present a review and synthesis of the hydrological and sedimentological knowledge of the Casiquiare River, including the first hydro-sedimentary balance of the Casiquiare fluvial system conducted at the bifurcation and at the mouth on September 9-12, 2000, during the expedition ‘Humboldt-Amazonia 2000’. Bathymetric, flow discharge and physico-chemical measurements were made at the inlet and at the outlet of the Casiquiare Channel. The main conclusions of this study indicate that Casiquiare is taking a significant proportion of flow (20 to 30%) from the Upper Orinoco basin to the Amazon basin. Throughout its 356 km-course, this chameleon channel undergoes significant morphological, hydrological and bio-geochemical variations between the inlet and the outlet, whose most visible witnesses are the increase in its width (3 to 4 times), flow (7 to 9 times) and its change in water color (white to black water), under the influence of tributaries coming from vast forest plains.