Cytokines are essential proteins that exert potent control over entire cell populations to fight infections and other pathologies, but can by themselves cause disease. Therefore, cytokine-related drugs act either by stimulating or blocking their activities. Our knowledge of the structures of cytokine-receptor complexes, the biophysical basis of their binding, and their mode of biological activation has substantially increased in recent years. This knowledge has been translated into new drugs and drug candidates. This review summarizes our current understanding of the receptor-mediated activity of cytokines, their relation to health and disease, and the agents in use to activate and block their actions. © 2010 Elsevier Ltd.