Reactivation of hepatitis B virus (HBV) infection has been described in patients with HBsAg negative and antiHBc positive (occult hepatitis B infection -OBI) receiving immunosuppressive therapy (IST). The lack of proper monitoring of patients with this HBV infection during IST can result in viral reactivations with high level of transaminases, jaundice and even acute liver failure. In these situations, it is mandatory to start antiviral therapy with nucleot(s) ide analogs (NA) which produce a strong viral suppression. We report a series of five cases of OBI patients with severe HBV reactivation during IST. One patient was diagnosed with hematologic malignancy (non-Hodgkin lymphoma), two with rheumatoid arthritis, one with psoriasis and one patient with renal transplant. All the patients were evaluated and treated for the reactivation of HBV in the Prof. Dr. Matei Bals National Institute of Infectious Diseases, a tertiary care hospital from Bucharest, Romania. At the time of HBV reactivation diagnosis, 3 patients were asymptomatic and two developed jaundice. All had acute ALT flares (more than 10 times the upper limit of normal range - ULN), very high HBV viral loads and anti-HBc serum IgM antibodies. All patients were immediately treated with ETV 0.5 mg/day and if it was possible, IST was stopped. In all cases was obtained quickly HBsAg loss under antiviral therapy.