Purpose of review A number of chronic viral infections could be reactivated by immunosuppressive agents used in rheumatic diseases. In this review, we will focus on the complex effect of immunosuppressive agents, including biologic agents, on the natural course of chronic viral infections as well as an approach to the prevention and management of therapy-induced viral reactivation. Recent findings Chronic viral infections that are affected by immunosuppression in the setting of an underlying rheumatic disease include those due to hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, and latent infections from Epstein-Barr virus, JC virus, or varicella zoster virus. The most recent data of the effects of immunosuppressive agents are reviewed, with special emphasis on the effects of biologic therapies (anti-tumor necrosis factor, anti-B cell), on these viral agents. Summary Clinicians should be aware of the risk for viral reactivation of an underlying chronic viral infection during immunosuppressive therapy. Despite the existence of such risk, the presence of chronic viral infection is not a contraindication to immunosuppressive therapy, given that appropriate pretherapy screening and close monitoring is applied.