The term "cytokine storm" refers to an excessive or uncontrolled release of proinflammatory cytokines, which can lead to severe and often fatal outcomes in various infectious and noninfectious diseases. The concept has gained significant attention in both scientific and popular media, but a clear definition and understanding of the molecular events leading to cytokine storms remain elusive. This review aims to define the cytokine storm and its biological consequences, focusing on respiratory viruses. It highlights how high-throughput genomic methods are revealing new insights into the cytokine storm, including the kinetics of cytokine gene expression and the redundancy and overlap in cytokine signaling. Cytokines are small proteins that play crucial roles in intercellular signaling and immune responses. Key cytokines associated with cytokine storms include interferons (IFNs), interleukins (ILs), chemokines, colony-stimulating factors (CSFs), and tumor necrosis factors (TNFs). These cytokines have diverse functions, from controlling cell proliferation and differentiation to regulating immune and inflammatory responses. The balance between proinflammatory and anti-inflammatory cytokines is critical for maintaining immune homeostasis, and disruptions in this balance can lead to cytokine storms. The cytokine storm is characterized by a systemic inflammatory response that can result in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In severe infections, the local inflammation spreads throughout the body, leading to systemic sepsis and organ dysfunction. The intensity of the inflammatory response is influenced by genetic factors, such as variations in Toll-like receptor (TLR) genes, which can predispose individuals to more severe cytokine storms. Genomic studies have provided valuable insights into the cytokine storm, revealing the dynamic transcriptional responses and the kinetic properties of cytokine and chemokine gene expression. For example, highly pathogenic influenza viruses aberrantly regulate cytokine and chemokine transcriptional responses, leading to a cytokine storm. The hyperresponsiveness of pattern recognition receptors (PRRs) and differential host proinflammatory responses also contribute to the severity of cytokine storms. Targeting the cytokine storm is a promising approach to reduce the self-inflicted damage caused by the host immune response. However, the complexity of the immune system and the challenges in developing effective therapies make this a challenging task. The review emphasizes the need for further research to better understand the cytokine storm and develop therapeutic strategies to prevent or mitigate its effects.The term "cytokine storm" refers to an excessive or uncontrolled release of proinflammatory cytokines, which can lead to severe and often fatal outcomes in various infectious and noninfectious diseases. The concept has gained significant attention in both scientific and popular media, but a clear definition and understanding of the molecular events leading to cytokine storms remain elusive. This review aims to define the cytokine storm and its biological consequences, focusing on respiratory viruses. It highlights how high-throughput genomic methods are revealing new insights into the cytokine storm, including the kinetics of cytokine gene expression and the redundancy and overlap in cytokine signaling. Cytokines are small proteins that play crucial roles in intercellular signaling and immune responses. Key cytokines associated with cytokine storms include interferons (IFNs), interleukins (ILs), chemokines, colony-stimulating factors (CSFs), and tumor necrosis factors (TNFs). These cytokines have diverse functions, from controlling cell proliferation and differentiation to regulating immune and inflammatory responses. The balance between proinflammatory and anti-inflammatory cytokines is critical for maintaining immune homeostasis, and disruptions in this balance can lead to cytokine storms. The cytokine storm is characterized by a systemic inflammatory response that can result in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In severe infections, the local inflammation spreads throughout the body, leading to systemic sepsis and organ dysfunction. The intensity of the inflammatory response is influenced by genetic factors, such as variations in Toll-like receptor (TLR) genes, which can predispose individuals to more severe cytokine storms. Genomic studies have provided valuable insights into the cytokine storm, revealing the dynamic transcriptional responses and the kinetic properties of cytokine and chemokine gene expression. For example, highly pathogenic influenza viruses aberrantly regulate cytokine and chemokine transcriptional responses, leading to a cytokine storm. The hyperresponsiveness of pattern recognition receptors (PRRs) and differential host proinflammatory responses also contribute to the severity of cytokine storms. Targeting the cytokine storm is a promising approach to reduce the self-inflicted damage caused by the host immune response. However, the complexity of the immune system and the challenges in developing effective therapies make this a challenging task. The review emphasizes the need for further research to better understand the cytokine storm and develop therapeutic strategies to prevent or mitigate its effects.