Humanized Mice as a Tool to Study Sepsis—More Than Meets the Eye

(1) Background. Repetitive animal studies that have disappointed upon translation into clinical therapies have led to an increased appreciation of humanized mice as a remedy to the shortcomings of rodent-based models. However, their limitations have to be understood in depth. (2) Methods. This is a narrative, comprehensive review of humanized mice and sepsis literature to understand the model’s benefits and shortcomings. (3) Results: Studies involving humanized models of sepsis include bacterial, viral, and protozoan etiology. Humanized mice provided several unique insights into the etiology and natural history of sepsis and are particularly useful in studying Ebola, and certain viral and protozoan infections. However, studies are relatively sparse and based on several different models of sepsis and humanized animals. (4) Conclusions. The utilization of humanized mice as a model for sepsis presents complex limitations that, once surpassed, hold some potential for the advancement of sepsis etiology and treatment.