Hepatitis B reactivation can occur in patients with inactive chronic hepatitis B receiving rituximab treatment. Therefore, hepatitis B virus (HBV) screening is recommended in patients planned for chemotherapy and antiviral prophylaxis needs to be started prior to initiating the treatment in patients with evidence of HBV infection. We describe a 58-year-old African American man with history of chronic hepatitis B who developed severe (HBV) reactivation while receiving rituximab treatment for Non-Hodgkin's lymphoma (NHL). The report highlights that greater education is needed amongst clinicians regarding risk of HBV reactivation while receiving chemotherapy, particularly with rituximab-based treatment.