The term “cytokine storm” calls up vivid images of an immune system gone awry and an inflammatory response flaring out of control (Fig. 1). The term has captured the attention of the public and the scientific community alike and is increasingly being used in both the popular media and the scientific literature. However, while the general concept of an excessive or uncontrolled release of proinflammatory cytokines is well known, an actual definition of what constitutes a cytokine storm is lacking. Furthermore, there is not a good understanding of the molecular events that precipitate a cytokine storm, of the contribution such a “storm” makes to pathogenesis, or of what therapeutic strategies might be used to prevent the storm or quell it once it has started.