Pityriasis rosea is an acute, self-healing exanthem characterized by oval erythematous-squamous lesions of the trunk and limbs, that usually spares face, scalp, palms, and soles. Constitutional symptoms, which have the character of true prodromes; clinical features, which resemble those of the known exanthems; and many epidemiologic data all suggest an infectious origin. A host of infectious agents have been incriminated, but, recently, human herpesvirus 6 and 7 have been extensively studied. The goal of this review is to outline the epidemiologic, clinical, histologic, and ultrastructural features of pityriasis rosea, but mainly to stress its possible human herpesvirus nature. In addition, clues have been added to help the reader to go through the complex subtleties of the virologic investigation.