Notch signalling has an important role in the immune system in directing cell fate decisions in a range of diverse cell types. We are beginning to obtain a better understanding of the roles that the different Notch ligands and receptors play in both cellular differentiation of precursor cells and the regulation of immune responses by mature lymphocytes in the periphery. This review will examine the key findings that have emerged in relation to function of Notch in differentiation of T cells, B cells and dendritic cells and how modulation of Notch signalling seems to have potential for therapeutic applications in immune based diseases.