Immunology grew as a medical science towards the end of 19th century. It was soon accepted that immunity involves both celluler and humoral factors. Early enough a Noble Prize (1908) was shared on the field, between Metchnikoff (discovery of phagocytosis) and Ehrlich (research in serology). Ehrlich, father of the side chain theory, introduced the term complement in 1899 to what Buchner had named alexin and Bordet had supported as the sensitizing substance. They all believed it owned bacteriolytic activity which was the result for two elements’ action, a stable, cytophilic group (antibody) on microbe or other cell and a heat sensitive substance (complement). Finally, the classical complement pathway was described In 1900. Soon, the complement fixation test brought revolution to the serological diagnosis of many bacterial infections (Bordet, Nobel Prize in medicine 1919). By the time, complement components were revealed and characterized in the serum. Scientists have worked over decades to determine the sequence of events due to complement system function, so that today three pathways of activation are recognized, the classical, the lectin and the alternative. For the regulation of complement activation and the prevention of tissue damage, certain inhibitory substances were created by host, such as C1INH, factors Ι /Η, DAF, CD46, CD59 and proteins CFHRs. Complement pathways, receptors and regulators will be briefly discussed below. In 1968, WHO committee established the order of events in complement component activation to C1, C4, C2, C3, C5–C9. Nowadays, it is well known that complement is involved in many diseases of autoimmune origin, in sepsis and SIRS, in transplantation, severe trauma, ischemia-perfusion injury and many others. Drugs for specific inhibition of complement components are under investigation after clinical benifit with eculizumab (monoclonal antibody that binds C5 and prevents cleavage by convertases).