The aquatic North American river otter (Lontra canadensis), a charismatic nonendangered mustelid, presently occupies a greatly reduced range. The species is common in zoos and has economic value as a furbearer. At least 17 states and one Canadian province have undertaken recent reintroduction programs. Nevertheless, little has been published on nonparasitic diseases of river otters, and little is known of the clinical significance of most of their parasitic infections. Records of environmental contaminant-related diseases and traumatic injuries in free-ranging North American river otters are also rare. This paper reviews present knowledge of North American river otter diseases, especially those with the greatest potential for impacting reintroduction programs.