Background. There are challenges in the clinical diagnosis of drug-induced injury and in obtaining information on the reactivation of human herpes viruses (HHV) during idiosyncratic adverse drug reactions. Objectives. (i) To develop a unified list of drugs incriminated in drug-induced hepatotoxicity and severe cutaneous reactions, in which drug hypersensitivity leads to HHV-6 reactivation and further complication of therapy and recovery and (ii) to supplement the already available data on reporting frequencies of liver- or skin-induced cases with knowledge of individual case reports, including HHV-6 reactivation and briefly introducing chromosomally integrated HHV-6. Data Sources and Extraction. Drugs identified as causes of (i) idiosyncratic reactions, (ii) drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii) human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.