Ophidian serpentoviruses, initially referred to as nidoviruses, were first documented in captive pythons nearly 10 yr ago. Since then, much has been learned about these important pathogens, now classified in the subfamily Serpentovirinae of the family Tobaniviridae and representing important emerging pathogens that threaten captive snakes. Serpentoviral infections are best characterized in pythons (family Pythonidae), but have also been documented in boas (family Boidae) and colubrids (family Colubridae), as well as shingleback skinks (Tiliqua rugosa), veiled chameleons (Chamaeleo calyptratus), and Bellinger River snapping turtles (Myuchelys georgesi). Clinical signs include increased oral mucous secretion, oral mucosal reddening, dyspnea, anorexia, and weight loss. Subclinical infections can also occur, and multiple studies report a lack of correlation between clinical signs and the presence of serpentoviral nucleic acids in snakes. Lesions associated with serpentoviral infections predominantly occur in the upper respiratory and gastrointestinal tracts, but can also extend to the lungs. Microscopically, these lesions may consist of inflammation, epithelial proliferation, and proliferative interstitial pneumonia, which can be complicated by concurrent bacterial bronchopneumonia. The most common method of diagnosis is reverse transcriptase polymerase chain reaction to detect viral RNA, and oral/choanal swabs are reliable samples for ante- or postmortem diagnosis. Specific treatment protocols have not yet been described, and management is based on supportive care. This paper presents a narrative review of all serpentovirus publications to date with perspective from researchers working to further characterize these pathogens, with the goal of serving as a comprehensive clinical and diagnostic overview for clinicians, zoological curatorial staff, wildlife biologists, and hobbyists.