A wide variety of pathogens is transmitted from ticks to vertebrates including viruses, bacteria, protozoa and helminths, of which most have a life cycle that requires passage through the vertebrate host. Tick-borne infections of humans, farm and companion animals are essentially associated with wildlife animal reservoirs. While some flying insect-borne diseases of humans such as malaria, filariasis and Kala Azar caused by Leishmania donovani target people as their main host, major tick-borne infections of humans, although potentially causing disease in large numbers of individuals, are typically an infringement of a circulation between wildlife animal reservoirs and tick vectors. While new tick-borne infectious agents are frequently recognised, emerging agents of human tick-borne infections were probably circulating among wildlife animal and tick populations long before being recognised as clinical causes of human disease as has been shown for Borrelia burgdorferi sensu lato. Co-infection with more than one tick-borne infection is common and can enhance pathogenic processes and augment disease severity as found in B. burgdorferi and Anaplasma phagocytophilum co-infection. The role of wild animal reservoirs in co-infection of human hosts appears to be central, further linking human and animal tick-borne infections. Although transmission of most tick-borne infections is through the tick saliva, additional routes of transmission, shown mostly in animals, include infection by oral uptake of infected ticks, by carnivorism, animal bites and transplacentally. Additionally, artificial infection via blood transfusion is a growing threat in both human and veterinary medicine. Due to the close association between human and animal tick-borne infections, control programs for these diseases require integration of data from veterinary and human reporting systems, surveillance in wildlife and tick populations, and combined teams of experts from several scientific disciplines such as entomology, epidemiology, medicine, public health and veterinary medicine. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.