There are a large number of drugs inducing headache as an adverse reaction. Nevertheless, headaches as adverse reactions to drugs have received limited attention. Non-serious adverse reactions, such as headache, are not quantified and described as accurately as serious, life threatening ones. However, non-serious reactions can also be extremely troublesome, above all when they are chronic: they can affect patients’ quality of life and contribute to non-compliance. It is absolutely possible that the number of patients with headache as an adverse reaction, which is going to increase, considering the growing use of medications. Physicians should, therefore, be aware of this issue. Indeed, it is difficult to attribute the diagnosis of adverse drug reaction to a condition, headache, which is also a very common symptom in general population.