This chapter focuses on the genera Anaplasma and Ehrlichia. Typically, antigenically variable proteins are immunodominant and thus allow evasion of the predominant immune responses. The donor allele repertoire remains unchanged during antigenic variation, while the expression-site variant is lost. This method is employed by some rickettsiae in the family Anaplasmataceae and allows for lifelong persistence in the host with donor allele repertoires 10- to 100-fold smaller than those found in African trypanosomes. Earlier work has demonstrated that major surface proteins (MSP)2 and MSP3 are immunodominant, antigenically variable proteins that are instrumental in evading the host immune response. Anaplasma ovis, a small ruminant pathogen, has been shown to establish persistent infections in goats. Antigenic variation in A. phagocytophilum is effected through the homolog of A. marginale msp2. The antibody response to the MSP2 HVR is variant specific and diminishes rapidly, consistent with the idea that antigenic variation of MSP2 is responsible for persistence. Research shows that the implications of donor allele repertoires go beyond antigenic variation in the individual hosts, and that they also play critical roles in the epidemiology of pathogen strain structure and possibly host tropism.