For many pathogens the role of antibody-mediated immunity (AMI) is poorly understood, in part because of the limited tools available to establish antibody efficacy. AMI is classically associated with opsonization, toxin and viral neutralization, complement fixation and antibody-dependent cellular cytotoxicity. However, recent studies indicate new functions for AMI ranging from direct antimicrobial action to modulation of the inflammatory response. The efficacy of AMI against some pathogens is dependent on cell-mediated immunity. A new interpretation of the role of AMI is proposed whereby it is in proinflammatory the early stages of infection and anti-inflammatory at later stages of the host–microbe interaction and in the setting of established immunity and/or in an immune individual.