Many of the pathogens responsible for diseases that result in both economic and global health burdens are transmitted by arthropod vectors in the course of a blood meal. In the past, these vectors were viewed mainly as simple delivery vehicles but the appreciation of the role that factors in the saliva of vectors play during pathogen transmission is increasing. Vector saliva proteins alter numerous physiological events in the skin; in addition, potent immunomodulatory properties are attributed to arthropod saliva. The description of specific factors responsible for these activities and their mechanisms of action have thus far remained mostly anecdotal. The National Institute of Allergy and Infectious Diseases (NIAID) sponsored a workshop in May 2012 to explore novel approaches aimed at identifying how vector saliva components affect the function of various immune cell subsets and the subsequent impact on the transmission of vector‐borne pathogens. Such knowledge could guide the development of novel drugs, vaccines and other strategies to block the transmission of vector‐borne pathogens. This meeting report summarizes the discussions of the gaps/challenges which represent attractive research opportunities with significant translational potential.