The genus Anaplasma includes a diverse group of tick-borne pathogens found exclusively within membrane-bound vacuoles in host cells. While A. marginale, A. centrale and A. ovis, vectored by Dermacentor and Rhipicephalus ticks, are host-specific for ruminants, A. phagocytophilum, vectored by Ixodes spp., infects a wide range of hosts. In ticks Anaplasma undergoes a developmental cycle that is coordinated with the tick feeding cycle. Although research at the tick/Anaplasma interface is in its infancy, recent studies have provided evidence that Anaplasma infection and transmission is mediated by a molecular mechanism involving both tick cell and pathogen genes. Application of a growing array of molecular approaches, such as RNA interference, genomics and proteomics, are rapidly expanding our knowledge of the tick/pathogen interface. Targeting key tick cell molecules required for pathogen development in vaccine strategies may compromise the vector capacity of ticks for Anaplasma, thus reducing transmission and infection of vertebrates. Collectively, this information will likely lead to the development of dual target vaccines designed to protect vertebrates against tick infestations and prevent the transmission of pathogens.