The tick-borne rickettsial pathogen Anaplasma phagocytophilum develops within membrane-bound inclusions in the host cell cytoplasm. This pathogen has evolved with its tick and vertebrate hosts through dynamic processes involving genetic traits of the pathogen and hosts that collectively mediate pathogen infection, development, persistence, and survival. Herein, we challenge the evidence of tick–host–pathogen coevolution by hypothesizing that A. phagocytophilum utilizes common molecular mechanisms for infection in both vertebrate and tick cells, including remodeling of the cytoskeleton, inhibition of cell apoptosis, and manipulation of the immune response. The discovery of these common mechanisms provides evidence that a control strategy could be developed targeted at both vertebrate and tick hosts for more complete control of A. phagocytophilum and its associated diseases.