The traditional in vitro correlate of immunological protection is the induction by a vaccine of neutralizing antibodies against the virus. It was formerly assumed that protection induced by a vaccine was solely due to neutralizing antibodies. Neutralizing antibodies are potent in the prevention of certain diseases, but virus-specific CD4+ T helper cells aid in the proliferation of specific antigen-triggered B cells to make antibodies. CD8+ T cells are responsible for eliminating virus-infected cells during viral illness, and may act as a second line of defence by becoming activated and eliminating any cells that become infected despite the presence of neutralizing antibodies, for example because of a large challenge dose or antigenic variation at the antibody combining sites. We will briefly review our approaches for measuring human virus-specific CD4+ and CD8+ T cell responses to experimental vaccines. It is critically important to have sensitive, quality controlled assays, including positive controls. There are many potential variables in human T cell assays and pitfalls, which usually result in negative CTL results. Uninterpretable data are to be expected unless adequate preliminary testing has been done to establish sensitive, specific and controlled human antigen specific CD4+ and CD8+ T cell assays.