Chlamydiae growing in target mucosal human epithelial cells in vitro can transition from their normal developmental cycle progression, alternating between infectious but metabolically inactive elementary bodies to metabolically active but noninfectious reticulate bodies (RBs) and back to elementary bodies, into a state of persistence. Persistence in vitro is defined as viable but noncultivable chlamydiae involving morphologically enlarged, aberrant, and nondividing RBs. The condition is reversible, yielding infectious elementary bodies after removal of the inducers, including penicillin, interferon-gamma, iron or nutrient starvation, concomitant herpes infection, or maturation of the host cell into its physiologically differentiated state. All aberrant RB phenotypes are not the same, owing to differing up- or down-regulated chlamydial gene sets and subsequent host responses. Although all persistence-inducing conditions exist in vivo, key questions include (1) whether or not aberrant chlamydial RBs occur in vivo during the alternating acute-silent chronic-acute chlamydial infection scenario that exists in infected patients and animals and (2) whether such aberrant RBs can contribute to prolonged, chronic inflammation, fibrosis, and scarring.