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Sepsis is a disease that has been known and studied for over 2000 years and yet there is still so much of it we do not understand. Our ignorance is not for lack of effort, however. In just the year 2015, PUBMED listed over 1400 articles published with sepsis as a major topic. The journey to understand sepsis over the years has been a microcosm of our progress all fields of medicine. It began as a common disease with varying outward manifestations and has progressed to become understood as problem that encompasses organs, cells, organelles, cytokines, molecules, and genetics of every part of the body. No longer just a clinical puzzle, it is now studied and discussed in papers ranging from molecular biology, to health services research and it remains a serious concern for practitioners of all branches of medicine.