Histologically, drug eruptions may present virtually all patterns of inflammation in the skin, including spongiotic, lichenoid and psoriasiform dermatitis as well as vasculitis or panniculitis. Drug reactions may mimic specific skin diseases such as lupus erythematosus, lichen planus or lymphoma. While a single drug may cause a wide range of reaction patterns, no reaction pattern is specific for a certain drug. Nevertheless, some reactions are quite characteristic for certain drugs as for example psoriasiform dermatitis for anti-TNF agents or folliculitis for epidermal growth factor receptor antagonists. Heightened awareness to the possible mimicry of other skin diseases as well as integration of clinical data is pivotal for the appropriate histological diagnosis of drug reactions in the skin. For practical reasons and in the aim of helping clinicians, the different drug reactions described in this chapter are classified according to the main histological reaction pattern present. Nevertheless, this classification may be somewhat artificial in some cases as drug reactions often reveal a coexistence of different reaction patterns.