In the last few decades it has been reported that the intake of some drugs may lead to the onset of a leg ulcer. In the etiology particularly allergic and toxic mechanisms have been postulated to induce pathological reactions which potentially lead to vasculitis or vasculopathies. The causal association of the intake of drugs and the occurrence of a leg ulcer is not always clearly proven. Most of the presented drugs in this overview are substances for which only a few case reports has been described for an association with leg ulcers. Diagnoses are often made by exclusion of other causes and because of a temporal relationship. One exception is drugs which contain the active ingredient hydroxyurea. More than 100 published patients have developed leg ulcers while on hydroxyurea. Moreover, these ulcerations have a typical clinical morphology. Numerous systemic medicaments can lead directly or indirectly to the onset of a leg ulcer. Therefore it is important to recognize this potentially relevant factor and adjust the medications as part of the therapeutic plan.