Two dogs with systemic nocardiosis are presented and the pathobiology, diagnosis, and treatment of nocardial infections are discussed. Both dogs had nonspecific respiratory signs and depression. The diagnosis was made by isolation of the organism only after surgical drainage was established and appropriate tissues were cultured. The response to surgical drainage and antimicrobial therapy was dramatic in both dogs, but one dog experienced a drug reaction to trimethoprim-potentiated sulfonamide. Although systemic nocardial infections traditionally have had a grave prognosis, through early diagnosis, surgical intervention, and the use of newer, safer and synergistically acting antimicrobials, the prognosis has improved. This article reviews current human and veterinary literature regarding the microbiology, pathogenesis, and treatment of nocardiosis and reports on the successful treatment of systemic nocardiosis in two dogs.