Despite the development of modern intensive care and new antimicrobial agents, the mortality of the patients with severe sepsis and septic shock remains high. The poor outcome is considered to be a consequence of an overactive systemic inflammatory response. Sepsis is now defined as systemic inflammatory response syndrome (SIRS) in which there is an identifiable focus of infection. As a consequence of the overactive SIRS response, the function of various organ systems may be compromised, resulting in multiple organ dysfunction syndrome (MODS) and death. Systemic inflammation is a consequence of activation of the innate immune system. It is characterized by intravascular release of pro-inflammatory cytokines and other vasoactive mediators, and the concurrent activation of the innate immune cells. In addition to the pro-inflammatory reactions, the host's anti-inflammatory mechanisms are also activated and aimed at counteracting the inflammatory response. The balance between pro- and anti-inflammatory reactions is critical for the outcome of the patient. Understanding the mechanisms of acute inflammatory responses in critical ill patients is necessary for the development of urgently needed therapeutics. The aim of this review is to provide a description of the key components and mechanisms involved in the inflammatory response in patients with SIRS and sepsis.