Intense research efforts so far have not been sufficient to reduce leishmaniasis burden worldwide. This disease is transmitted by bites of infected sand flies, which inject saliva in the host skin in an attempt to obtain a blood meal. Sand fly saliva has an array of proteins with diverse pharmacological properties that modulates the host homeostatic and immune responses. Some of these proteins are also immunogenic and can induce both cellular and humoral immune responses. Recently, the use of sand fly salivary proteins to estimate exposure to sand fly bites and consequently the risk of infection has emerged. Here, we review evidence that supports the use of the host immune responses against sand fly salivary proteins to estimate risk of infection. We also discuss how the use of recombinant salivary proteins can optimize serological surveys and provide guidance for the implementation of specific measures for disease control in endemic areas