A safe and effective vaccine to prevent tuberculosis is necessary to combat this ancient disease that kills millions worldwide. Recent advances in our understanding of the host immune response to Mycobacterium tuberculosis (Mtb) are facilitating the development of several novel vaccine approaches. New tools for measuring and characterizing cell-mediated immune responses to Mtb have furthered the assessment of these new vaccines in animal models and in human clinical studies including efficacy trials. Measurements of the relative contribution of CD4+ and CD8+ T cells, central and effector memory T cells, and regulatory T cells are being completed in these studies, as well as broad screening efforts utilizing bead array cytokine determination and microarray technology in an effort to determine the immunologic markers that predict vaccine-induced efficacy for different stages of TB infection and disease.