Sepsis continues to escape a precise diagnostic definition. The most recent consensus definition, termed Sepsis-3, highlights the importance of the maladaptive and potentially life-threatening host response to infection. After briefly reviewing the history and epidemiology of sepsis, we go on to describe some of the challenges encountered when classifying such a heterogenous disease state. In the context of these new definitions for sepsis and septic shock, we explore current and potentially novel therapies, and conclude by mentioning some of the controversies of this most recent framework.