Neutralizing antibodies are a major component of host defense against viruses, and appear to be particularly important in limiting the spread of cell-free virus. Results from vaccine trials in animal models suggest that these antibodies may contribute to protection against human immunodeficiency virus (HIV) infection. Here, Pascal Poignard and colleagues discuss recent developments in this area, with particular emphasis on the measurement, specificity and mechanism of the antibody response, and its significance for vaccine production.