The first cases of DIHS were described almost 70 years ago, but so far elucidation of its aetiopathogenesis has remained a challenge for researchers. DIHS can be distinguished from other types of drug eruptions by the limited number of culprit drugs, delayed onset in relation to the introduction of causative medication and also clinical similarity to infectious mononucleosis. Besides the undoubtedly crucial role of exposure to the causative drug, it seems that another important element of DIHS pathogenesis is reactivation of human herpes virus-6 (HHV-6) and possibly other viruses included in this group. DIHS patients present an increased level of anti-viral IgG after approximately 3 weeks from the onset of symptoms, and furthermore viral DNA can be detected in patients’ blood and skin using PCR and hybridization in situ. Apart from skin lesions, DIHS is characterized by internal organ involvement: liver, spleen, kidneys and lungs. Despite the fact of variable course of DIHS, most treated patients improve and recover usually within months. Management of DIHS includes (apart from essential withdrawal of the suspected drug) glucocorticoid therapy, antiviral agents and in some cases also intravenous immunoglobulin pulse therapy and plasma exchange.