Migraine patients with frequent and severe headaches need prophylaxis. The most used approach is monotherapy, i.e. one of the available preventive compounds is prescribed to the patient, testing its efficacy and tolerability during a treatment period of some months. Some clinicians use to add a second (or even a third) preventive compound to improve the effects of pharmacological prophylaxis, using an approach that can be defined as polytherapy. In this paper, the main advantages of monotherapy are briefly reviewed, taking into account several aspects: published evidence on polytherapy; the possibility to evaluate the adverse events of the prescribed treatment and to assess its real efficacy; the possibility of addressing different patient's needs, particularly the treatment of comorbidities and the development of an effective patient-physician communication.