Human herpes virus-6 was first reported in 1986 and is the sixth member of the herpes virus family. HHV-6 consists of two closely related variants HHV-6A and HHV-6B. The majority of infections occur in healthy infants with most infections caused by HHV-6B. The virus preferentially infects CD4+T-lymphocytes and the surface marker CD46 acts as a co-receptor. Infection is followed by persistence and latency in different cells and organs including monocytes/macrophages, salivary glands, the brain and the kidneys. In this article we will discuss the clinical manifestations of HHV-6 infection in healthy children and the syndromes associated with HHV-6 reactivation in immunocompromised patients. Evidence of association between HHV-6 infection and different clinical entities such as multiple sclerosis, malignancy, infectious momononucleosis, drug hypersensitivity syndromes and skin eruptions is discussed. Published data on the use and efficacy of antiviral agents in complicated infections and infections in immunocompromised patients is presented.