Although CD8 T-cell vaccines do not have the record of success of humoral-mediated vaccines, they do not receive the same degree of effort. Many diseases, including malaria, tuberculosis, and acquired immune deficiency syndrome (AIDS) have not yielded to vaccines, and intrinsic barriers may impede approaches limited solely to generating antibodies. Moreover, population growth and modernization are driving an increased pace of new emerging global health threats (human immunodeficiency virus [HIV] is a recent example), which will create unpredictable challenges for vaccinologists. Vaccine-elicited CD8 T cells may contribute to protective modalities, although their development will require a more thorough understanding of CD8 T-cell biology, practices for manufacturing and delivering CD8 T-cell-eliciting vectors that have acceptable safety profiles, and, ultimately, the political will and faith of those that make vaccine research funding decisions.