Ticks can transmit many pathogens, including arboviruses, to their vertebrate hosts. Arboviruses must overcome or evade defense mechanisms during their passage from the tick gut to the hemolymph, salivary glands, and the feeding site in the host skin. This review summarizes current knowledge of defense mechanisms in specific tick tissues and at the feeding site in the host skin. We discuss the possible roles of these defense mechanisms in viral infection and transmission. The responses of tick salivary proteins to arbovirus infection are also discussed. This review provides information that may help accelerate research on virus-tick interactions.