Innate and adaptive immunity are required for effective control of infection. Numerous breakthroughs have been achieved in the last 15 years with regard to the functioning of the innate immune system. This article focuses on new paradigms of microorganism recognition, discusses recently described (or rediscovered) cytokines that provide further insight into the development of sepsis, and reviews both pro- and anti-inflammatory pathways for control of infection. Finally, it discusses what has and has not worked with regard to controlling inflammatory pathways in septic patients.