Immune recognition of antigens usually relies on the interaction of multiple antibody loops. Ekiert et al. identified an antibody (from a patient who survived H5N1 infection) that recognized a conserved region of the receptor binding site on the haemagglutinin (HA) protein through an interaction that was mediated by a single heavy-chain complementarity-determining region 3 loop. The antibody bound H1, H2, H3, H9 and H12 HA, and when given prophylactically or therapeutically to mice it protected against lethal challenge with H1N1 or H3N2 types of influenza A. Single-loop antibodies that target small conserved regions might be therapeutically exploited to achieve broad neutralization of influenza.