Neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases. They probably act, in most cases, by blunting the infection, which is then resolved by cellular immunity. The protective effects of neutralizing antibodies can be achieved not only by neutralization of free virus particles, but also by several activities directed against infected cells. In certain instances, non-neutralizing antibodies contribute to protection. Several viruses, such as HIV, have evolved mechanisms to evade neutralizing-antibody responses, and these viruses present special challenges for vaccine design that are now being tackled.