Cytokines of the beta-common (bc) family, namely granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5, are regulators of normal and malignant haemopoiesis and have recently shown to act outside the haemopoietic system. These cytokines bind to specific heterodimeric receptors consisting of a cytokine specific a-subunit and the bc subunit, which interacts with all three cytokines. Overexpression of the bc cytokines has been linked to many diseases, such as leukaemia and inflammation [1]. As such, the shared use of the bc subunit by GM-CSF, IL-3 and IL-5 makes it an attractive focus of investigation for novel therapeutics that would disrupt the interaction of all three cytokines with their receptors. We have thus used the crystal structure of the bc subunit, solved in complex with GM-CSF and its a-subunit [2, 3], to identify inhibitors of the interaction between GM-CSF and the bc subunit. These inhibitors will also aid in understanding the downstream signalling pathways activated by the βc family heterodimeric receptors and may elucidate new targets for drug discovery. Thus, we have investigated the interaction between the βc subunit with binding partners such as Janus Kinase 2, which binds to the intracellular domain of the βc subunit and subsequently activates various pathways promoting cell survival, proliferation and myeloid cell activation [4]. We have also investigated βc interactions with the erythropoietin receptor (EPOR), which forms a heterodimer with the βc subunit and contributes to tissue protection and healing in vivo [5]. It is thought that different, yet overlapping signalling pathways are activated by the EPOR-βc and the cytokine-βc receptor complexes. We are currently trying to understand how one signalling pathway switches to the other. The outcomes of these studies may ultimately form the basis for the development of new treatments in various clinical scenarios linked to the βc receptor.