Cytokine signalling is dependent on the activation of signal transducer and activator of transcription (STAT) proteins. Activation entails the tyrosine phosphorylation of STATs and their formation of dimers that are retained in the nucleus. These dimers are thought to constitute a diffusible pool in the cell nucleus, from which they are either recruited to DNA and function as transcription regulators, or they are dephosphorylated and resume nucleo-cytoplasmic shuttling. Our research has demonstrated that this model of STAT protein functioning in the nucleus needs to be amended. We have discovered that activated STAT dimers can polymerize and assemble higher-order structures in the nucleus of cytokine-stimulated cells. STAT polymerization can take place both on DNA and in the nucleoplasm. STAT polymers are highly dynamic, with components in constant flux with the surrounding nucleoplasm, whereby DNA-independent polymers can align laterally, leading to well-ordered structures and transition to a liquid crystal-like phase. In contrast to probably all other STAT family members, DNA-independent polymerization of STAT1 can be suppressed by SUMO conjugation. In conjunction with the ability of different STATs to co-polymerize, STAT supramolecular structures may thus constitute a structural base for the cross-regulation of cytokine signal pathways. We have begun to characterize STAT polymerization and its consequences for cytokine signalling. Our results show that phase transitions associated with STAT supramolecular assembly affect cytokine signalling in important ways, examples of which will be presented.