The pathogenic potential of spirochetes and their significance in the development of oral diseases, as well as in infections in other organs, have gained new interest for several reasons. First, these bacteria have the potential to be pathogenic because of their number and frequency at infected sites, their production of tissue irritants, their ability to invade tissues, their abundance in mixed infections, and their methods to evade host defense mechanisms. Second, of the microbial species that are associated with oral infections, spirochetes are infectious agents that cause severe diseases in other body sites. Third, during the past few years, new techniques have made it possible to obtain more information about spirochetes at the genetic level. Thereby, we have gained better knowledge of these bacteria, even though many cannot be cultured in the laboratory yet. Such knowledge includes the diversity of oral species as well as antigenic similarities between the species commonly found in the oral cavity and known pathogens such as the syphilis agent Treponema pallidum subsp. pallidum, Lyme disease agents Borrelia burgdorferi sensu lato group, and the swine dysentery agent Brachyspira (Serpulina) hyodysenteria. This review covers the main areas of what is known to date about Treponema. It focuses especially on factors related to their taxonomy, epidemiology, and biology, with special emphasis on their presence and possible role in endodontic infections.