Multidose regimens are recommended for all prophylactic subunit vaccines. Recent findings from clinical trials of an human papillomavirus virus-like particle vaccine suggest that it may be possible to develop effective single-dose subunit vaccines. The broad implications of these findings are discussed, and the importance of antigen structure and adjuvant in achieving this goal is considered. In conclusion, we argue for the inclusion of single-dose arms in future trials of vaccines, especially if they are based on induction of antibodies by virus-like displayed antigens.