Successful therapy based on the use of interferon-alpha has been reported in different types of severe chronic uveitis. The immunomodulatory effects of this drug, combined with its antiviral properties seem to contribute to its efficacy in the treatment of different forms of severe and refractory uveitis such as Vogt-Koyanagi-Harada disease, Behçet-associated uveitis, or even human herpes virus 8 (HHV-8) associated uveitis. At the same time, severe ocular complications have been reported in patients treated with interferon-alpha for chronic viral hepatitis C. Among these complications, six cases of Vogt-Koyanagi-Harada-like disease have been described.We report a small case series of two patients with refractory Vogt-Koyanagi-Harada disease, treated with interferon-alpha and discuss the potential benefits or detrimental role of interferon therapy in these patients.