Interferon-based therapies are associated with various neuropsychiatric side effects, and poorly controlled psychiatric disease is an absolute contraindication to interferon and ribavirin therapy. However, treatment of HCV infection in patients with stable psychiatric disease is controversial. Emerging data, such as the study by Jakiche and colleagues in this issue of The American Journal of Gastroenterology, provide additional evidence that HCV-infected patients with stable psychiatric disease can safely be treated with interferon and ribavirin therapy. Multidisciplinary collaboration between HCV providers and mental health professionals will help to make HCV treatment a viable option for the large number of patients with stable psychiatric disease.