Ticks (Acari: Ixodidae) transmit a wide variety of pathogens to vertebrates including viruses, bacteria, protozoa and helminthes. Tick-borne pathogens are believed to be responsible for more than 100,000 cases of illness in humans throughout the world. Ticks are considered to be second worldwide to mosquitoes as vectors of human diseases, but they are the most important vectors of disease-causing pathogens in domestic and wild animals. Infection and development of pathogens in both tick and vertebrate hosts are mediated by molecular mechanisms at the tick-pathogen interface. These mechanisms, involving traits of both ticks and pathogens, include the evolution of common and species-specific characteristics. The molecular characterization of the tick-pathogen interface is rapidly advancing and providing new avenues for the development of novel control strategies for both tick infestations and their associated pathogens.