The complement system is an integral part of innate immunity and is chiefly responsible for controlling bacterial infections, especially those involving gram- negative organisms. To accomplish this task, serum proteins engage in a series of enzymatic cascades. The cleaved proteins assemble pores on membranous structures, which lead to cell lysis. During this process, powerful inflammatory mediators are produced, including the anaphylatoxins, C5a, C3a, and the membrane attack complex (MAC). Under systemic inflammatory conditions, an overactive complement system may compromise the effectiveness of innate immunity. We review the detrimental effects that are caused by uncontrolled complement activation during sepsis.