The classes of medications for migraine treatment are numerous and include ergots, triptans, NSAIDs, antidepressants, anti-epilepsy drugs, antihypertensives and natural supplements. Physicians need to be aware not only of medication efficacy but also of tolerability and safety. Side effects of these drugs can sometimes be beneficial, as migraineurs frequently have comorbid conditions. For example, those with insomnia can benefit from use of a tricyclic antidepressant that is effective in preventing migraine. However, these same coexistent conditions can be worsened by migraine medication or be contraindicated and multiple medications prescribed for several conditions can result in drug-drug interactions. This article reviews adverse events associated with migraine and medications, and their implications in clinical treatment.