It is now recognized that sepsis is not a uniformly proinflammatory state. There is a well-recognized counter anti-inflammatory response that occurs in many patients. The timing and magnitude of this response varies considerably and thus makes its identification and manipulation more difficult. Studies in animals and humans have now identified a small number of biologic responses that characterize this immunosuppressed state, such as lymphocyte death, HLA receptor downregulation, and monocyte exhaustion. Researchers are now trying to use these as markers of individual immunosuppression to predict outcomes and identify patients who would and would not benefit from new immune stimulatory therapies.