In this issue of Critical Care Clinics, guest editors Drs. Manu Shankar-Hari and Lieuwe D. J. Bos bring their considerable expertise to the topic of Sepsis and Systemic Inflammatory Syndromes. Sepsis and systemic inflammatory syndromes represent life-threatening medical emergencies and remain leading causes of morbidity and mortality worldwide. Advances in early detection, biomarker development, and targeted immunomodulatory therapies continue to reshape clinical practice, making this issue especially timely for clinicians in emergency medicine, critical care, and multiple medical specialties.