Headache is among the most common neurological symptoms in clinical practice. In some cases of episodic migraine, the headache intensifies into a chronic form, defined as chronic migraine (CM) and such a condition encompasses a headache frequency of 15 days/month, with features similar to those of migraine attacks. The assessment of CM in the US general population ranges around 1.3-2%. Migraine progression from an episodic into a chronic form is realized through a period of time involving several months or years, during which an increase attack frequency occurs. Both Topiramate and Onabotulinum toxin A can be considered to be safe as well as effective medications, therefore, representing a treatment choice. Regarding drug abusers, the initial relief step always consists of drug interruption. Only after detoxification can a new prophylaxis therapy be commenced, which otherwise would be useless from the start. The feasible diagnostic setting for the tailored treatment of CM based on the application of pharmacogenomics will allow us in predetermining the efficacy of a single old and new drugs by avoiding abuse due to non-responsivity of the abused drug.