Historically, antibody-mediated immunity was considered effective against toxins, extracellular pathogens and viruses, while control of intracellular pathogens was the domain of cellular immunity. However, numerous observations in recent decades have conclusively shown that antibody can protect against intracellular pathogens. This paradigmatic shift has tremendous implications for immunology and vaccine design. For immunology the observation that antibody can protect against intracellular pathogens has led to the discovery of new mechanisms of antibody action. For vaccine design the knowledge that humoral immunity can be effective in protection means that the knowledge acquired in more than a century of antibody studies can be applied to make new vaccines against this class of pathogens.