It is clear that resistance against acute tuberculosis (TB) is dependent on the host's ability to generate Th1 immunity. Nevertheless, the role of host immunity in latent TB remains incompletely defined. Recent progress in elucidating host innate and adaptive immune responses to M. tuberculosis (Mtb) and their impact on latent infection includes identification of TLR2-dependent anti-inflammatory responses, a MyD88-independent, non-protective Th1 response, the formation of secondary lymphoid follicles in granulomas and the role of Th1 responses, IFN-gamma and TNF-alpha in preventing re-activation of infection; IFN-gamma also appears to be involved in activating latency genes in Mtb. When Mtb re-infects a patient, it appears to localize in established granulomas; however, different bacterial strains may behave differently. Although these advances do not provide all the answers regarding host defense mechanisms, they nevertheless bring us closer to new and better design strategies for immunotherapy and immunoprophylaxis.