Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks, enhance response to acute medications, improve patient function and reduce disability. Sufficient evidence and consensus exist to recommend propranolol, timolol, amitriptyline, pizotifen, divalproex, sodium valproate and topiramate as first line agents for migraine prevention. These drugs can halve the frequency of attacks in 50% of patients. The anticipated benefit must be weighed against the adverse effects associated with each agent in determining the optimal preventive regimen for individual patients considering any comorbid conditions that are often present. The decision to treat and the choice of prophylactic drug must be taken with the patient. It is important to balance expectations and therapeutic realities for each particular drug. Recent data on the effect of prophylactic treatment on trigeminovascular activation and on cortical spreading depression emphasise the importance of developing research on migraine-preventive drugs.