HHV-6, the first T-lymphotropic human herpesvirus, is an important novel human pathogen. It is the cause of exanthem subitum in infants and may act as an opportunistic agent in immunocompromised patients. Moreover, several lines of clinical and experimental evidence suggest that HHV-6 may accelerate the progression of HIV infection. Progress in the study of HHV-6 has been rapid, in part as a consequence of the strong current interest in human lymphotropic viruses and their relationship with the immune system. Nonetheless, the full spectrum of diseases linked to this agent is still unknown (Table 2) and animal models of infection have not yet been exploited. The next few years will be crucial for a complete understanding of the potential role of HHV-6 in human disease.