Sepsis and sepsis-associated multi-organ failure are significant challenges for healthcare systems and clinicians. Despite extensive research, the pathophysiology of sepsis remains poorly understood. This review highlights recent insights into the molecular interactions during sepsis and aims to unravel the dysregulated immune response. Sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the inflammatory network. The clinical manifestations of sepsis have been recognized since ancient times, but the understanding of its pathogenesis has evolved over centuries. Recent studies have shown that sepsis involves a complex interplay of biological systems and cell types, leading to severe dysregulation of the inflammatory network. Key mediators such as C5a, macrophage migration-inhibitory factor (MIF), high-mobility group box 1 protein (HMGB1), and interleukin-17 (IL-17) play central roles in this network. The complement system, coagulation cascade, and autonomic nervous system (ANS) also contribute to the pathogenesis of sepsis. Targeting these pathways may offer therapeutic opportunities, but the complexity of the inflammatory response in sepsis requires further research to develop effective treatments.Sepsis and sepsis-associated multi-organ failure are significant challenges for healthcare systems and clinicians. Despite extensive research, the pathophysiology of sepsis remains poorly understood. This review highlights recent insights into the molecular interactions during sepsis and aims to unravel the dysregulated immune response. Sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the inflammatory network. The clinical manifestations of sepsis have been recognized since ancient times, but the understanding of its pathogenesis has evolved over centuries. Recent studies have shown that sepsis involves a complex interplay of biological systems and cell types, leading to severe dysregulation of the inflammatory network. Key mediators such as C5a, macrophage migration-inhibitory factor (MIF), high-mobility group box 1 protein (HMGB1), and interleukin-17 (IL-17) play central roles in this network. The complement system, coagulation cascade, and autonomic nervous system (ANS) also contribute to the pathogenesis of sepsis. Targeting these pathways may offer therapeutic opportunities, but the complexity of the inflammatory response in sepsis requires further research to develop effective treatments.