The complement system was first described in the late 19th century as the property of fresh serum to cause in vitro cell death after agglutination. It represents the oldest identified component of the immune system. The complement system consists of a series of about 20 different serum proteins that are part of the body's first-line, innate immune defenses (Figure 1). As such, the complement system is a triggered cascade of highly amplified proteolytic reactions ultimately leading to enhanced adherence of offending microorganisms, stimulation of more effective inflammation and phagocytosis, and direct lysis of the offending cells. The complement system is divided into two pathways on the basis of the trigger of the complement cascade. The classic pathway is activated when C1 binds to the Fc fragment of IgM or IgG in immune complexes. The inactive C1 molecule has three subunits—C1q, C1r, and C1s—that are held together by ionic calcium. The C1q component binds to immunoglobulin in the immune complex. With the binding of C1q, C1r undergoes enzymatic cleavage of its two subunits, exposing active proteolytic sites. The activated proteolytic site on C1r cleaves the C1s peptide, exposing its active enzymatic site. In turn, activated C1s acts as a protease for both C4 and C2. With the activation of C4 and C2 into C4b,2a complex, the C3 convertase enzyme is created (Figure 1). The activation of the alternate complement pathway is somewhat less clear. It involves the activation of C3 by a C3-convertase complex consisting of C3b,Bb. Under normal circumstances, low levels of turnover of C3 to C3b take place. During inflammation, low levels of C3b bind factor B, which then undergoes enzymatic cleavage by factor D to generate C3b, Bb. This in turn acts as a potent C3 convertase, amplifying the complement cascade. Therefore, successful generation of a C3-convertase enzyme complex is central to the process of complement activation by either pathway.