This review covers relevant clinical and laboratory information relating to Epstein-Barr virus (EBV) infections in immunocompromised hosts. It describes the epidemiology and clinical manifestations with a primary focus on disease in solid organ and stem cell transplant recipients. The review pays particular attention to diagnostic approaches, including serologic testing and imaging, with an expanded discussion on the role of measuring the EBV load in peripheral blood, identifying both strengths and limitations of this assay. Additional attention is paid to potential additional strategies of immunologic monitoring that may enhance the performance of EBV load monitoring.