This review provides a comprehensive summary of the current understanding of the global burden of sepsis and septic shock. Sepsis is a life-threatening condition caused by a dysregulated host response to infection, leading to organ dysfunction. Despite advancements in medical care, sepsis and septic shock remain major global health burdens with high morbidity and mortality rates. The review highlights significant variations in the incidence, prevalence, and mortality rates of sepsis and septic shock across different countries and regions, with low- and middle-income countries (LMICs) being disproportionately affected. Risk factors, comorbidities, and challenges in clinical management and diagnosis are discussed in various healthcare settings. The review emphasizes the need for further research, increased awareness, and context-specific interventions to address the global burden of sepsis and septic shock. The definition of sepsis has evolved over time, with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) introducing a more precise definition emphasizing organ dysfunction and the host response. The epidemiology of sepsis and septic shock varies significantly by continent, with higher incidence rates in LMICs due to factors such as limited access to healthcare, delayed diagnosis, and the prevalence of infectious diseases. Mortality rates are also higher in LMICs, highlighting the need for improved healthcare resources and evidence-based management practices. Risk factors for sepsis include age, sex, chronic health conditions, and acute medical or surgical conditions. Environmental and socioeconomic factors also play a significant role in the global burden of sepsis, with poverty, inadequate sanitation, and limited access to healthcare contributing to higher incidence rates in LMICs. The diagnosis and clinical management of sepsis vary across healthcare settings, with challenges in low-resource environments including limited access to diagnostic tools and trained healthcare professionals. Effective diagnosis and treatment require context-specific strategies, including the use of clinical scoring systems and improved access to antimicrobial therapy and source control measures. The economic burden of sepsis and septic shock is substantial, with significant direct and indirect costs impacting both developed and developing countries. Prevention strategies, quality improvement initiatives, and antimicrobial stewardship programs are essential to reducing the global burden of sepsis. Challenges in global sepsis management include the lack of uniform diagnostic standards and treatment strategies, the need for context-specific interventions, and the importance of improving healthcare infrastructure and access to essential resources. Future directions in sepsis management include the development of context-specific diagnostic criteria, the use of biomarkers, and the implementation of effective quality improvement programs to enhance patient outcomes.This review provides a comprehensive summary of the current understanding of the global burden of sepsis and septic shock. Sepsis is a life-threatening condition caused by a dysregulated host response to infection, leading to organ dysfunction. Despite advancements in medical care, sepsis and septic shock remain major global health burdens with high morbidity and mortality rates. The review highlights significant variations in the incidence, prevalence, and mortality rates of sepsis and septic shock across different countries and regions, with low- and middle-income countries (LMICs) being disproportionately affected. Risk factors, comorbidities, and challenges in clinical management and diagnosis are discussed in various healthcare settings. The review emphasizes the need for further research, increased awareness, and context-specific interventions to address the global burden of sepsis and septic shock. The definition of sepsis has evolved over time, with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) introducing a more precise definition emphasizing organ dysfunction and the host response. The epidemiology of sepsis and septic shock varies significantly by continent, with higher incidence rates in LMICs due to factors such as limited access to healthcare, delayed diagnosis, and the prevalence of infectious diseases. Mortality rates are also higher in LMICs, highlighting the need for improved healthcare resources and evidence-based management practices. Risk factors for sepsis include age, sex, chronic health conditions, and acute medical or surgical conditions. Environmental and socioeconomic factors also play a significant role in the global burden of sepsis, with poverty, inadequate sanitation, and limited access to healthcare contributing to higher incidence rates in LMICs. The diagnosis and clinical management of sepsis vary across healthcare settings, with challenges in low-resource environments including limited access to diagnostic tools and trained healthcare professionals. Effective diagnosis and treatment require context-specific strategies, including the use of clinical scoring systems and improved access to antimicrobial therapy and source control measures. The economic burden of sepsis and septic shock is substantial, with significant direct and indirect costs impacting both developed and developing countries. Prevention strategies, quality improvement initiatives, and antimicrobial stewardship programs are essential to reducing the global burden of sepsis. Challenges in global sepsis management include the lack of uniform diagnostic standards and treatment strategies, the need for context-specific interventions, and the importance of improving healthcare infrastructure and access to essential resources. Future directions in sepsis management include the development of context-specific diagnostic criteria, the use of biomarkers, and the implementation of effective quality improvement programs to enhance patient outcomes.