The means by which pathogens suppress, subvert, or elude host defenses and establish latent infections include microbially induced immunosuppression or antigenic variation, gaining access to sites of the body that are inaccessible to the immune system, and manipulating of the immune response to the advantage of the pathogen. Various risk factors of the host, such as immunosuppression, may be crucial in determining the frequency with which latency is the outcome of primary infection, as well as the likelihood that subsequent reactivation occurs. Mechanisms of reactivation of latent infections may also be triggered by disruption of anatomic or ecologic barriers, or through the cooperative efforts of a second pathogen. Although viruses, due to their unique ability to incorporate their genetic material into host genomes, are best known for their capacity for persistence, examples of latency can be found among all classes of microorganisms. The clinical and epidemiological importance of microbial latency is enormous, because such infections represent potential reservoirs from which dissemination of pathogens to new susceptibles can occur, because they may reactivate to cause acute or chronic progressive disorders in the original host, and because such infections might play a role in the origin of some human cancers. Few areas of basic research hold greater promise of substantially contributing to our understanding of infectious diseases and the eventual relief of human suffering.