Chronic daily headache (CDH) affects approximately 4 to 5% of the population and encompasses a number of different diagnoses, including transformed migraine, chronic tension-type headache (TTH), new-onset daily persistent headache, and hemicrania continua. Although the pathophysiology of CDH is still poorly understood, some research has suggested that each of the various subtypes of CDH may have a different pathogenesis. The goals of prophylactic therapy are to reduce the frequency, severity, and duration of headache attacks; to improve responsiveness to treatment of acute attacks; to improve function; and to reduce disability. However, opinions differ as to exactly which are the best and most appropriate outcome measures for prophylaxis. Several pharmacologic treatment options exist, including antidepressants, anticonvulsants, muscle relaxants, serotonin agonists, ergots, serotonin antagonists, antianxiety agents, and other miscellaneous drugs. Tizanidine, an alpha(2)-adrenergic agonist, has recently emerged as a promising prophylactic adjunct for CDH, which implicates a central alpha(2)-adrenergic mechanism as an important factor in the pathophysiology of CDH.