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Infections with cytomegalovirus (CMV) cause significant morbidity and mortality following hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT). The impact of this infection on transplantation extends beyond the direct effects of its dissemination in blood and invasion of target organs to so-called ‘indirect effects’ that include increased incidence of other opportunistic infections and reduced graft and patient survival. Significant efforts have been implemented in diagnosis, prevention and treatment of these infections, which have resulted in increased resource utilization and overall cost. With the effective use of sensitive tests for diagnosis and antiviral drugs for prevention, the incidence of CMV infection and disease has been reduced. However, antiviral drug resistance and late-onset CMV disease are emerging concerns. Additionally, the newer members of the β-herpesvirus subfamily – human herpesvirus (HHV)-6 and HHV-7 – are being recognized as important pathogens or co-pathogens following SOT and HSCT. Like CMV, HHV-6 and HHV-7 have direct effects that result from their invasion of target organs. More importantly, their impact on transplantation may result ‘indirectly’ from their interaction with CMV and their modulating effect on the immune system. Increased predisposition to opportunistic infections such as CMV disease and invasive fungal infection has been described among patients with HHV-6 infection. It is anticipated that the advances in diagnostic modalities for the detection and quantification of HHV-6 and HHV-7 replication will uncover the clinical spectrum of their pathogenic potential during the post-transplantation period. This review article assesses the current scientific data on the impact that the β-herpesviruses have on the outcomes of HSCT and SOT.