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Complex systems science has led to valuable insights regarding the care and understanding of critical illness, but has not led to fundamental improvements to care to date. Realizing the fact that there is inherent uncertainty in patient trajectory, we have developed Continuous Individual Multiorgan Variability Analysis (CIMVA) as a tool theoretically and practically designed to track the systemic emergent properties of the host response to injury or infection. We present an overview of CIMVA software, and discuss four separate potential clinical applications that we are evaluating; including early detection of infection, better prediction of extubation failure, continuous monitoring of severity of illness in the ICU, and the evaluation of cardiopulmonary fitness. Future challenges are discussed in conclusion.