Although specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody-dependent enhancement of bacterial infection is largely unrecognized. Recently, we demonstrated that in a significant portion of patients with Pseudomonas aeruginosa lung infection and bronchiectasis or cystic fibrosis, antibody can protect the bacterium from serum- and cell-mediated killing (J Exp Med. 2014 211:1893-904). Patients with impaired serum-mediated killing of P. aeruginosa had poorer respiratory function than infected patients who do not produce inhibitory antibody. In vitro assays of serum-mediated killing revealed that depletion of inhibitory antibody restores the ability of sera to kill strains. Based on these observations, patients with bronchiectasis were treated with plasmapharesis to remove inhibitory antibodies. Pseudomonas aeruginosa infection resolved in patients treated by plasmapharesis and remained undetectable while titres of inhibitory antibody remained low. These findings have marked implications for our understanding of protection generated by natural infection, for the design of vaccines and for treatment of patients with bronchiectasis and cystic fibrosis.