The differentiation of B- and T-cells in primary lymphoid organs depends on, or is strongly influenced by, signals provided by stromal cells, extracellular matrix components as well as by direct contacts between differentiating lymphocytes and distinct environmental cells. Notch receptors and their ligands mediate intercellular contacts and are crucially important for the development of T- and B-cell lineages. Here we start by reviewing current knowledge on the expression patterns of Notch receptors and their ligands in primary lymphoid organs and the effects induced by their functional interactions. Then we shall attempt to discuss how those interactions may regulate not only lymphopoiesis per se but also morphogenesis and the functional compartmentalization of lymphopoietic organs during development.