Nocardia asteroides as an infecting agent has been an increasingly identified pathogen in humans, especially in immunosuppressed hosts. The Nocardia organisms as a cause of septic arthritis have been very unusual and in all previously reported cases have occurred in immunosuppressed patients. This is a report of two additional patients, one of whom has had no history of immunosuppression either before infection or subsequent to treatment and resolution of the infection. The second is a case of a questionably immunosuppressed patient with Nocardia asteroides septic arthritis. These cases reemphasize the importance of performing not only the most common aerobic and anaerobic bacterial cultures but also fungal and acid-fast bacilli cultures for early identification of less common organisms and for the initiation of appropriate therapy.