Cytokines participate in the induction and effector phases of all immune and inflammatory responses. They are therefore obvious tools and targets for strategies designed to promote, inhibit or redirect these responses. However, the complexity of the cytokine network has hindered the widespread clinical application of many cytokines and it has become clear that a deeper understanding of the normal operation of this system in health and disease is needed for the therapeutic potential of cytokines to be fully realized. This review summarizes some of the principles that are now thought to underlie the diverse functions of the interleukins, interferons, colony-stimulating factors and tumour necrosis factors in immune and inflammatory reactions in vivo. Genetic and structural relationships between these cytokines, the regulation of their synthesis, and the structures and functions of their receptors are outlined. Current knowledge of these parameters suggests ways in which multiple positive and negative regulatory mechanisms are integrated to balance cytokine benefits and harm under physiological conditions and offers new prospects for rational exploitation of this system.