Species of the Cannabis plant genus were among the earliest medicinal plants cultivated by man, with historical accounts of their medicinal uses dating back before the Common Era. Despite its current legal status, Cannabis has garnered nationwide attention as a therapeutic agent for various disease states, including chronic headaches, due to its medical indications as an antispastic, analgesic, antiemetic, neuroprotective and anti-inflammatory agent. Since headaches have a high prevalence in the American population and greatly impair simple daily aspects of living, chronic headaches have become a particular point of interest in regard to the therapeutic potential of Cannabis. Clinical trials and case reports have shown that Cannabis administration for headaches has greatly improved the quality of life and decreased the use of adjuvant medications for some patients. Studies are limited and conflicting, mostly due to the legal issues associated with Cannabis. Pharmacists play a major role in managing patients who are treating their chronic headaches and need to be able to educate patients about Cannabis. Patients may consider trying to treat their headaches with Cannabis even though it has legal restrictions regarding its use and is not U.S. Food and Drug Administration (FDA) approved. Pharmacists should understand federal and state restrictions, drug interactions, potential health risks, psychoactive effects and types of delivery systems for Cannabis use.