The first recognized outbreak of pneumonia due to Legionella pneumophila occurred in Philadelphia in July of 1976 among 180 persons attending the 56th annual American Legion Convention. Twenty nine patients died, and the disease became known as Legionnaires’ disease (Fraser et al., 1977). Guinea pigs were infected with postmortem lung tissue from the patients with fatal Legionnaires’ disease, and embryonated yolk sacs were inoculated with spleen homogenates from the infected guinea pigs. In January of 1977, a gram-negative bacterium was isolated and designated L. pneumophila (McDade et al., 1977). Antisera were subsequently generated which facilitated identification of many previous outbreaks of febrile respiratory illness of unknown etiology that occurred since 1965. The source of the infection during the Legionnaires’ convention was later found to be the air conditioning system in the hotel. It has been documented that the hallmark of Legionnaires’ disease is the intracellular replication of L. pneumophila in the alveolar spaces. At least another 39 species of legionellae have been identified, some of which are associated with disease while others are environmental isolates and whether they can cause disease is not known. L. pneumophila is responsible for more than 80% of cases of Legionnaires’ disease, and among the 13 serogroups of L. pneumophila, serogroup 1 is responsible for more than 95% of Legionnaires’ disease cases. It is estimated that L. pneumophila is responsible for at least 25,000 cases of pneumonia/year in the US. In 1980, Rowbotham described the ability of L. pneumophila to multiply intracellularly within protozoa (Rowbotham, 1980). Since then, L. pneumophila has been described to multiply in many species of protozoa, and this host-parasite interaction is central to the pathogenesis and ecology of L. pneumophila. Intracellular replication of L. pneumophila within mammalian and protozoan cells has been shown to occur in a ribosome-studded phagosome that does not fuse to lysosomes. Fields had hypothesized that the L. pneumophila phagosome fuses to the rough endoplasmic reticulum (RER) (Fields, 1993). Immunocytochemistry has proven this prediction by demonstrating the presence of an RER-specific chaperon, the Bip protein, in the ribosome-studded phagosome within macrophages (Swanson and Isberg, 1995), and protozoa (Abu Kwaik, 1996). Based on these characteristics the L. pneumophila phagosome may be accurately described as endosomal maturation-blocked (EMB) phagosome.KeywordsAlveolar Epithelial CellAlveolar SurfaceIntracellular SurvivalIntracellular InfectionIntracellular ReplicationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.