The exacerbation of a co-existing autoimmune disease is often a concern for physicians who use immunomodulating agents for the treatment of a concomitant process. As physicians begin to treat chronic hepatitis C more often and more aggressively, this potential problem with occur more frequently. Herein we reported a case of reactivation of sarcoidosis occurring during the treatment of chronic hepatitis C, and we present a literature review of other centers' experiences with this problem. Depending upon the severity of the exacerbation and the type of organ involvement, reactivation of sarcoidosis may require discontinuation of the interferon therapy, with or without the use of additional steroids. The majority of patients, however, do not require the use of steroids. Interestingly, continuation of the interferon therapy in the presence of a mild-to-moderate exacerbation of sarcoidosis may be safe in a minority of patients with noncritical organ involvement.