Research in the past decade has led to the recognition of Brachyspira (formerly Serpulina) pilosicoli as the primary etiologic agent of colonic spirochetosis (CS), an emerging cause of colitis in humans and animals. Attachment of spirochetes to the epithelial surface of the lower intestine is considered to be the hallmark of CS. However, because B. pilosicoli, B. aalborgi and unclassified flagellated bacteria are found singly or together in humans and non-human primates with CS lesions, attachment of spiral-shaped bacteria may not represent the same etiopathogenetic entity in all hosts. Moreover, North American opossums with CS are infected with B. aalborgi-like spirochetes together with flagellated bacteria, whereas B. pilosicoli is found alone in dogs, pigs, chickens and other species of birds with CS. Conversely, guinea-pigs with CS have unidentified spirochetes that may be B. pilosicoli or B. aalborgi. The pig model of CS suggests that attachment of B. pilosicoli to epithelial cells may be transient. By contrast, persistence of B. pilosicoli in the cecal and colonic crypt lumina, chronic inflammation caused by spirochetal invasion into the subepithelial lamina propria and translocation to extraintestinal sites may be more important than previously thought. This review describes the lesions seen in naturally occurring and experimentally induced CS of animals, and it sets the stage for future research into the pathogenic mechanisms of infection and colitis caused by B. pilosicoli.