Prevention is an important aspect of HIV care in the era of highly active antiretroviral therapy. Vaccines provide an excellent opportunity to avert certain infectious diseases for which patients with HIV infection are at increased risk due to immunosuppression. However, the state of immunosuppression reduces the efficacy of vaccines and increases the risk associated with certain vaccines. The study of vaccine responses in patients with HIV infection has greatly advanced the understanding of the underlying immune deficits, particularly with regards to reduced CD4 cell number and function and the level of immune activation associated with chronic viremia. This research has also solidified the safety and utility of vaccines for this population. Continued research of vaccine responses will further our understanding of the immune system and optimize the utilization of routine immunizations.