Tuberculosis (TB) remains a major global health problem and subunit vaccines for the control of the disease are presently under development. This vaccine strategy requires an in vitro correlate of protection for the identification of relevant vaccine candidate antigens and for monitoring the induction of a protective cell-mediated immune response after vaccination. New studies of experimental vaccines in the mouse model of TB support interferon-γ as a relevant marker for the induction of a protective immune response. In contrast, searching for immunodominant antigens capable of inducing strong interferon-γ responses in PPD positive healthy or TB infected individuals may not identify all relevant candidate antigens for inclusion in a novel TB subunit vaccine.