A series of substudies of a large international cytomegalovirus (CMV) prophylaxis trial investigated the incidence and clinical relevance of reactivation of human herpesviruses 6, 7, and 8, varicella zoster virus, Epstein-Barr virus, polyomavirus, and adenovirus, and the effect of CMV prophylaxis on clinical and subclinical non-CMV viral infections, in adult solid organ transplant (SOT) patients. Results of the substudy analyses showed that viremia caused by a number of viruses is surprisingly common posttransplantation; most of these infections likely represent reactivation of endogenous latent virus. In addition, although infection or active viral replication was common in this cohort of SOT patients, symptomatic disease due to these viruses was uncommon and the clinical sequelae of viremia were unclear or not apparent. CMV prophylaxis may have modified the natural history of some of these non-CMV viral infections.