Sepsis is caused by a dysregulated host response to infection. Immune responses determine the characteristics of sepsis. The body's protection against infection involves danger signal surveillance and recognition from nonself, effector functions in response to sensing danger signals, homeostatic regulation, and generation of immunologic memory. During sepsis, the immune system is activated by pathogen-associated and host-derived molecular patterns. Detecting these molecular patterns generates multisystem responses. Impaired organ function remote to the site of infection is the unifying feature. The processes by which an appropriate response to a microbial invader change from adaptive to maladaptive and dysregulated remain unclear.