During host defense, the human complement system of plasma proteins initiates inflammatory and cellular immune responses to stimuli such as infectious organisms, chemical and physical injury, radiation and neoplasia. Elevated levels of one of these plasma proteins C5a, a 74 amino acid peptidic anaphylatoxin which is one of the most potent pro-inflammatory agents, correlate with the initiation and development of many inflammatory diseases. New agents which prevent binding of C5a to its G-protein-coupled receptors can inhibit the pro-inflammatory actions of C5a and thus be potentially used to treat chronic inflammatory disorders driven by complement activation and C5a production. In recent years significant progress has been made towards the development of potent antagonists of human C5a receptors and clinically useful compounds can reasonably be expected within the next few years.