The article "Advances and Challenges in Sepsis Management: Modern Tools and Future Directions" by Santacroce et al. reviews the current understanding and management of sepsis, a critical condition characterized by systemic inflammation and profound immune alterations. The authors emphasize the importance of phenotyping in sepsis to enhance patient-specific diagnostic and therapeutic strategies. Flow cytometry is highlighted as a crucial tool for rapid, low-cost, and detailed analysis of immune cell populations and their functional states, aiding in the understanding of immune dysfunctions and the identification of novel biomarkers. The review underscores the potential of integrating flow cytometry with omics data, machine learning, and clinical observations to refine sepsis management, advocating for personalized medicine in critical care. The article also discusses the complex pathophysiology of sepsis, including molecular and immune mechanisms, and the impact on various organ systems. It explores the role of different immune cell subsets, such as neutrophils, monocytes, natural killer (NK) cells, γδ T cells, MAIT cells, T lymphocytes, and B lymphocytes, in sepsis. The metabolic shifts in immune cells, from hypermetabolic to hypometabolic states, are also discussed, highlighting the "hibernation theory" as a protective mechanism. Finally, the article addresses the challenges in sepsis therapy and the need for personalized approaches, emphasizing the importance of cell phenotyping in tailoring treatment strategies based on individual patient characteristics.The article "Advances and Challenges in Sepsis Management: Modern Tools and Future Directions" by Santacroce et al. reviews the current understanding and management of sepsis, a critical condition characterized by systemic inflammation and profound immune alterations. The authors emphasize the importance of phenotyping in sepsis to enhance patient-specific diagnostic and therapeutic strategies. Flow cytometry is highlighted as a crucial tool for rapid, low-cost, and detailed analysis of immune cell populations and their functional states, aiding in the understanding of immune dysfunctions and the identification of novel biomarkers. The review underscores the potential of integrating flow cytometry with omics data, machine learning, and clinical observations to refine sepsis management, advocating for personalized medicine in critical care. The article also discusses the complex pathophysiology of sepsis, including molecular and immune mechanisms, and the impact on various organ systems. It explores the role of different immune cell subsets, such as neutrophils, monocytes, natural killer (NK) cells, γδ T cells, MAIT cells, T lymphocytes, and B lymphocytes, in sepsis. The metabolic shifts in immune cells, from hypermetabolic to hypometabolic states, are also discussed, highlighting the "hibernation theory" as a protective mechanism. Finally, the article addresses the challenges in sepsis therapy and the need for personalized approaches, emphasizing the importance of cell phenotyping in tailoring treatment strategies based on individual patient characteristics.