A variety of different drugs has been associated with a rather distinct clinical illness characterised by skin rash, fever and single or multiple organ involvement, which starts within 8 weeks after the initiation of the therapy. There is no consensus in the denomination of this apparently distinct clinical entity so that the acronym DRESS (drug rash with eosinophilia and systemic symptoms) has been recently proposed to focus thinking on this particular and probably under-recognised subset of drug reaction. The aim of this review is to point to the new perspectives regarding the diagnosis, the physiopathology and the management of DRESS syndrome.