Diverse cytokines can signal through receptor complexes containing the gp130 subunit. These cytokines, which include interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), and CLC (cardiotrophin-like cytokine), are implicated in inflammatory and immune responses, heart development, and fertility. The gp130 receptor-ligand complexes are contrasted with the complex formed by erythropoietin (Epo) and its receptor, EpoR. Also discussed are insights provided by the structural analysis of IL-6, its alpha receptor (IL6Ralpha), and the signal transducer gp130 for understanding receptor-ligand assembly, for predicting the structures of ligand-receptor complexes of the other IL-6-type cytokines, and for rational drug design.