Ticks are the major arthropod vectors transmitting pathogenic agents to humans and domestic animals in Europe, and currently, the incidence of tick-borne disease is rising. The most common European human tick-borne disease is Lyme borreliosis, with an estimated 90 000 new cases every year (compared to 300 000 new cases in the United States annually). This disease is initially clinically diagnosed by the presence of migrating erythema following a tick bite, which is then subsequently confirmed by serological tests. In parallel with classic Lyme borreliosis cases, tick-bitten patients can also present with polymorphic and non-specific clinical symptoms (asthenia, fever, myalgia, etc. …) for which there is no known diagnosis It is extremely difficult to determine the proportion of tick-bitten patients with these symptoms compared to patients which have actually contracted Lyme disease, although it is estimated that 50% of fevers following a tick bite have an unknown infectious origin. The situation is similar for domesticated animals, particularly cattle and dogs which can contract infection from the same tick species as humans. In these animals, only one disease, babeosis, is recognized by veterinarians, however veterinarians and breeders are constantly reporting other tick-related problems and other undiagnosed diseases affecting both French herds and pets. Typical tick habitats are woodlands, prairies, pastures, and gardens. Ticks are extremely sensitive to environmental fluctuations, which are often brought about by human socio-economic changes, thus tick-borne diseases are excellent candidates for emergence. Consequently, it is incontestable that tick-borne diseases pose a significant threat to our society. In addition to improving diagnostic techniques, one of the major hurdles relates to improving public and health professional knowledge about tick disease risk. The battle against tick-borne diseases is based on relatively simple prevention measures, and their effectiveness is immeasurably improved when citizens are more informed and involved. Therefore, we have designed a multidisciplinary project, bringing together veterinarians, doctors, scientists, and consultant sociologists to create a global “One Health” approach to tick-borne diseases. Specific scientific project objectives are to (1) detect, identify, and isolate new microorganisms—both unknown or unexpected—from patients or animals suffering from unexplainable symptoms following tick bites; (2) to demonstrate tick competence in their ability to transmit these agents; and (3) to generate concrete recommendations to improve tick-borne disease management. Due to our multi-disciplinary consortium of experts, we are sure to achieve our goals of generating novel insights into tick-borne disease. These results will be invaluable in the development of novel and improved diagnostic tests, and for the generation and dissemination of up-to-date information to the public. This study will also encompass and promote improved training for veterinary and medical students. We will also generate detailed recommendations for public health authorities to improve overall management of tick-borne diseases.