M. tuberculosis remains one of the most successful human pathogens known. The causative agent of tuberculosis, it also has a unique ability to persist for years in the infected, apparently healthy host. This dormant organism can be reactivated years, even decades later to cause tuberculosis. Knowledge regarding the interaction of M. tuberculosis with the host is fundamental to understanding the pathogenesis, leading eventually to the development of strategies for the prevention and control of infection and disease. By integrating genetic, microbiologic, immunologic, and cell biologic approaches to elucidate pathogenesis, penetrating new insights into the interaction of M. tuberculosis with the host have emerged. This book reviews the most important state-of-the-art approaches currently used to study microbe-host interactions and highlights emerging methodologies. Strategies to analyze the following topics are included: mycobacterial entry, growth, and gene expression in macrophages; analysis of post-phagocytic events; analysis of signaling in infected macrophage; the acquired immune response; newer animal- and non animal-models systems; latency; and the epidemiology of M. tuberculosis infections.