Advances in technology—especially single-cell antibody cloning techniques—have led to the isolation and characterization of antibodies from people with HIV infection that can neutralize many variants (1). These are referred to as broadly neutralizing antibodies (bnAbs). Such antibodies can be detected in about 25% of persons with untreated HIV-1 infection (2), reflecting a host immune response to unremitting viral replication, generation of large numbers of viral variants, and shifting antigen exposure (3). Although bnAbs may exert some selective pressure as they develop, they generally do not reduce viral burden, improve health, or slow the progression of disease (4). However, they offer considerable opportunities for treatment and prevention of HIV-1 infection in others. At this time, hundreds of bnAbs have been identified; those that have attracted the most attention are bnAbs with the greatest breadth, neutralizing the largest number of HIV-1 strains, including those traditionally most neutralization resistant (1, 5); or bnAbs that have the greatest potency, requiring the smallest concentration to neutralize resistant strains of HIV-1 (5–7). A study by Xu et al. (5) on page 85 of this issue and by Julg et al. (7) in Science Translational Medicine illustrate advances in the potential use of bnAbs to prevent HIV-1 infection.