This chapter focuses on the strategies that persistent bacterial pathogens use to evade, subvert, and disarm the host immune system. Bacteria can avoid these host defense mechanisms by presenting the immune system with a continuously evolving antigen repertoire. Two related processes, antigenic variation and phase variation, generate molecular variants that escape antibody detection. The widespread human pathogen Mycobacterium tuberculosis has evolved stress resistance mechanisms that allow it to persist within the phagolysosome of activated macrophages. Bacterial biofilms are now recognized as the cause of many persistent infections that are refractory to antibiotic treatment. Some biofilm infections are associated with surfaces of medical devices such as catheters, shunts, prostheses, and mechanical heart valves. IL-10 is a potent anti-inflammatory and immunesuppressive cytokine that affects antigen presenting cells and T cells. For some bacterial pathogens, persistence in the host depends on the production of protein toxins that interfere with cellular physiology. Intoxication of antigen-presenting cells by CyaA may promote the expansion of regulatory T-cell populations and suppress immunity.