The use of broadly neutralizing antibodies against the influenza viral surface glycoprotein haemagglutinin (HA) represents a promising therapeutic approach. In mice, Shen et al. implemented several immunization regimens to induce cross-reactive antibodies against highly conserved epitopes in the HA protein of influenza B. A functional screening strategy identified the highly potent antibody C12G6, which targeted the receptor binding site in the HA region and inhibited influenza B viruses via multiple mechanisms. In vitro, C12G6 neutralized all available influenza B viruses isolated since 1940. Furthermore, C12G6 exhibited broad prophylactic and therapeutic activity in mice and ferrets.