Some bacterial pathogens can establish life-long chronic infections in their hosts. Persistence is normally established after an acute infection period involving activation of both the innate and acquired immune systems. Bacteria have evolved specific pathogenic mechanisms and harbor sets of genes that contribute to the establishment of a persistent lifestyle that leads to chronic infection. Persistent bacterial infection may involve occupation of a particular tissue type or organ or modification of the intracellular environment within eukaryotic cells. Bacteria appear to adapt their immediate environment to favor survival and may hijack essential immunoregulatory mechanisms designed to minimize immune pathology or the inappropriate activation of immune effectors.