Complement C5a is a pro-inflammatory polypeptide produced during activation of the complement cascade in response to foreign antigens or tissue damage secondary to physical or chemical injury. C5a, via activation of the C5a receptor (C5aR or CD88), is a major inflammatory mediator involved in a number of diseases, including some of veterinary relevance. Greater understanding of the role of C5a has been possible with the availability of gene knockout mice, specific antibodies and peptide agonists/antagonists. This review outlines the functions of C5a and its role in the development of disease, including neoplastic conditions and sepsis, in animals of veterinary importance. The application of C5aR agonist and antagonist analogues to combat those conditions is also discussed.