Skin is the main sufferer of the adverse drug reactions (ADRs), being involved in 30% of all ADRs cases. However, ADRs are generally underestimated because of the difficulty to correlate the event to a particular drug. A careful anamnestic history is crucial to establish the causal link between an ADR and the specific drug. Clinical, developmental and medical history is important to define an ADR but sometimes you need to make histological examination to get additional diagnostic indications. However, the histological findings observed during the ADRs are hardly or not easily distinguishable from other skin diseases. Furthermore, the patient is often administered multiple drugs, so that the evaluation of histological findings is a complex one. In the present work we have reviewed the most frequently reported histological pictures induced by drugs as associated with a specific ADR, following, as criterion, the localization of the damage within the skin. So ADRs are divided into reactions in which the damage is localized in the epidermis, at dermal-epidermal (junction) level, in the dermis, subcutaneous fat and adnexal structures. We then briefly describe the clinical and histological pictures most frequently observed in ADRs.