The prevention of HIV-1 by vaccination has proven to be a formidable task. In an ongoing endeavor to end the HIV-1 pandemic, scientists seek vaccines that will elicit quantitatively and qualitatively robust B-cell and T-cell activities. Given that cytotoxic T-lymphocytes (CTL) play a substantial role in the immunological control of immunodeficiency virus infections, this review will focus on vaccines designed to elicit HIV-1-specific CTL. Vaccine approaches using various HIV-1 proteins or specific CTL determinants, partnered with diverse delivery systems and adjuvants will be discussed. Lessons from studies with other virus models (e.g. gamma herpes virus and influenza virus) will also be examined. Since CTL contribute to the success of vaccines in other model systems, an understanding of the strengths and possible limitations of these cells may be critical to future successes in the HIV-1 vaccine field.