Tick-borne prokaryotic pathogens share a very intimate relationship with the vectors. Ingestion during the bloodmeal places the microbe into the gut lumen whence it must travel to the salivary glands at the right time for transmission during a subsequent feeding. This crucial event requires coordination between pathogen development and arthropod host activities that may be mediated by the expression of genes specific for the vector phase of the pathogen. Invertebrate hormones or factors associated with tick tissues may provide the cues that signal changes in tick physiology that induce necessary steps in the pathogen, such as colonization of ovaries during egg development in preparation for transovarial transmission or dispersion to the salivary glands at the time of a bloodmeal. These hypotheses cannot easily be investigated within the complex environment of the tick, but tick cell culture offers a simplified system with which to examine many of these important interrelationships.