Despite an urgent need for a prophylactic vaccine against human immunodeficiency virus (HIV) type 1, progress in this area has been slow. The initial euphoria after identifying and sequencing the causative agent of the acquited immunodeficiency syndrome (AIDS) was followed by a realization that for HIV, traditional vaccine approaches would not be applicable. Frustrations with the induction of neutralizing antibodies led to the development of new vaccine focusing on the induction of cytotoxic T-lymphocytes (CTLs). While CTLs cannot confer sterilizing immunity, there are encouraging data from animal models suggesting that these vaccines may increase the threshold of infection and delay the onset of AIDS in humans. The CTL hypothesis and the possibility that some non-neutralizing antibodies may assist CTLs in the prophylaxis against HIV have yet to be tested in phase III efficacy trials.